Author: "Institute of Metabolic Science" - Searchworks@Jio Institute Digital Library Search Results

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3,095 results on '"Institute of Metabolic Science"'

1. Regenerative Cellular Therapies, Physiology, Pathology and Developmental Biology (RCT)

Author: University of Cambridge, Cambridge Stem Cell Institute, Cambridge, Anne McLarent Laboratory of Regenerative Medicine, Cambridge, The Gurdon Institute, Cambridge, Sanger Institure, Cambridge, Institute of Metabolic Science, Cambridge, MRC Mitochondrial Biology Unit, Cambridge, and Dr. Kourosh Saeb-Parsy, Mr Kourosh Saeb-Parsy
Published: 2016

2. Advanced hybrid closed loop therapy versus conventional treatment in adults with type 1 diabetes (ADAPT): a randomised controlled study

Author: Pratik Choudhary, Ralf Kolassa, Winfried Keuthage, Jens Kroeger, Charles Thivolet, Mark Evans, Roseline Ré, Simona de Portu, Linda Vorrink, John Shin, Aklilu Habteab, Javier Castañeda, Julien da Silva, Ohad Cohen, King‘s College London, NHS Foundation Trust [London], The Royal Marsden, University of Leicester, Diabetologische Schwerpunktpraxis [Bergheim, Germany] (DS), Schwerpunktpraxis für Diabetes und Ernährungsmedizin [Münster, Germany] (SDE), Zentrum für Diabetologie Bergedorf [Hamburg, Germany] (ZDB), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), MRC Epidemiology Unit [Cambridge, UK] (Wellcome Trust-MRC Institute of Metabolic Science), University of Cambridge [UK] (CAM)-Addenbrooke’s Hospital [Cambridge, UK]-Wellcome Trust-MRC Institute of Metabolic Science (IMS), Medtronic Diabetes, International Trading Sàrl [Tolochenaz, Switzerland ] (MDITS), Medtronic [Northridge, CA, USA] (Mt), Medtronic Bakken Research Center BV, Institut de Ciencies del Cosmos (ICCUB), Universitat de Barcelona (UB), ADAPT study Group, and CarMeN, laboratoire
Subjects: Adult, Blood Glucose, Glycated Hemoglobin, Blood Glucose Self-Monitoring, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Diabetic Ketoacidosis, [SDV] Life Sciences [q-bio], Diabetes Mellitus, Type 1, Treatment Outcome, Endocrinology, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Prospective Studies
Abstract: International audience; BACKGROUND: Adults with type 1 diabetes who are treated with multiple daily injections of insulin plus intermittently scanned continuous glucose monitoring (isCGM) can have suboptimal glucose control. We aimed to assess the efficacy of an advanced hybrid closed loop (AHCL) system compared with such therapy in this population. METHODS: The Advanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes (ADAPT) trial is a prospective, multicentre, open-label, randomised controlled trial that involved 14 centres in three European countries (France, Germany, and the UK). We enrolled patients who were at least 18 years of age, had a type 1 diabetes duration of at least 2 years, HbA(1c) of at least 8% (64 mmol/mol), and were using multiple daily injections of insulin plus isCGM (cohort A) or real time continuous glucose monitoring (cohort B) for at least 3 months. Here, only results for cohort A are reported. Participants were randomly allocated 1:1 to AHCL therapy or continuation of multiple daily injections of insulin plus continuous glucose monitoring for 6 months with an investigator-blinded block randomisation procedure. Participants and treating clinicians could not be masked to the arm assignment. The primary endpoint was the between-group difference in mean HbA(1c) change from baseline to 6 months in the intention-to-treat population using AHCL therapy and those using multiple daily injections of insulin plus isCGM. The primary endpoint was analysed using a repeated measures random-effects model with the study arm and period as factors. Safety endpoints included the number of device deficiencies, severe hypoglycaemic events, diabetic ketoacidosis, and serious adverse events. This study is registered with ClinicalTrials.gov, NCT04235504. FINDINGS: Between July 13, 2020, and March 12, 2021, 105 people were screened and 82 randomly assigned to treatment (41 in each arm). At 6 months, mean HbA(1c) had decreased by 1·54% (SD 0·73), from 9·00% to 7·32% in the AHCL group and 0·20% (0·80) in the multiple daily injections of insulin plus isCGM from 9·07% to 8·91% (model-based difference -1·42%, 95% CI -1·74 to -1·10; p\textless0·0001). No diabetic ketoacidosis, severe hypoglycaemia, or serious adverse events related to study devices occurred in either group; two severe hypoglycaemic events occurred in the run-in phase. 15 device-related non-serious adverse events occurred in the AHCL group, compared with three in the multiple daily injections of insulin plus isCGM group. Two serious adverse events occurred (one in each group), these were breast cancer (in one patient in the AHCL group) and intravitreous haemorrhage (in one patient in the multiple daily injections of insulin plus isCGM group). INTERPRETATION: In people with type 1 diabetes using multiple daily injections of insulin plus isCGM and with HbA(1c) of at least 8%, the use of AHCL confers benefits in terms of glycaemic control beyond those that can be achieved with multiple daily injections of insulin plus isCGM. These data support wider access to AHCL in people with type 1 diabetes not at target glucose levels. FUNDING: Medtronic International Trading Sàrl.
Published: 2022

3. Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription

Author: Rebecca Bounds, Inês Barroso, Eleftheria Zeggini, Felicity Payne, Nicholas J. Wareham, Caroline Hayward, Elana Henning, Stephen O'Rahilly, Gaëlle Marenne, Elena G. Bochukova, Audrey E. Hendricks, Sofie Ashford, Allan Daly, Julia M. Keogh, I. Sadaf Farooqi, Saad Pathan, Aliki Perdikari, Eleanor Wheeler, Vanisha Mistry, Christopher J. Lelliott, Claudia Langenberg, The Wellcome Trust Sanger Institute [Cambridge], Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), University of Colorado [Denver], Metabolic Research Laboratories [Cambridge, UK] (University of Cambridge), Wellcome Trust - MRC Cambridge-Addenbrooke’s Hospital [Cambridge, UK], MRC Human Genetics Unit, University of Edinburgh-Western General Hospital, Generation Scotland [Edinburgh, UK] (Centre for Genomic and Experimental Medicine), University of Edinburgh-Institute of Genetics and Molecular Medicine [Edinburgh, UK], MRC Epidemiology Unit [Cambridge, UK] (Wellcome Trust-MRC Institute of Metabolic Science), University of Cambridge [UK] (CAM)-Addenbrooke’s Hospital [Cambridge, UK]-Wellcome Trust-MRC Institute of Metabolic Science (IMS), MRC Metabolic Diseases Unit [Cambridge, UK] (Metabolic Research Laboratories), University of Cambridge [UK] (CAM), Helmholtz Zentrum München = German Research Center for Environmental Health, marenne, gaelle, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), and Helmholtz-Zentrum München (HZM)
Subjects: Male, 0301 basic medicine, Pediatric Obesity, Pro-Opiomelanocortin, Physiology, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Bioinformatics, Mice, 0302 clinical medicine, Endocrinology, Missing heritability problem, Chlorocebus aethiops, Transcriptional regulation, Medicine, Exome, genetics, Child, Cells, Cultured, Exome sequencing, Genetics, Intracellular Signaling Peptides and Proteins, Imidazoles, POMC, Middle Aged, Penetrance, Obesity, Morbid, [SDV] Life Sciences [q-bio], Female, Adult, MEDLINE, Biology, Article, Childhood obesity, 03 medical and health sciences, gene set, Animals, Humans, severe childhood obesity, Molecular Biology, Gene, Genetic association, function, Genetic heterogeneity, business.industry, association, Genetic Variation, Cell Biology, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, business, 030217 neurology & neurosurgery
Abstract: Summary Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, we identified three genes (PHIP, DGKI, and ZMYM4) with an excess burden of very rare predicted deleterious variants in cases. In cells, we found that nuclear PHIP (pleckstrin homology domain interacting protein) directly enhances transcription of pro-opiomelanocortin (POMC), a neuropeptide that suppresses appetite. Obesity-associated PHIP variants repressed POMC transcription. Our demonstration that PHIP is involved in human energy homeostasis through transcriptional regulation of central melanocortin signaling has potential diagnostic and therapeutic implications for patients with obesity and developmental delay. Additionally, we found an excess burden of predicted deleterious variants involving genes nearest to loci from obesity genome-wide association studies. Genes and gene sets influencing obesity with variable penetrance provide compelling evidence for a continuum of causality in the genetic architecture of obesity, and explain some of its missing heritability., Graphical Abstract, Highlights • Three genes (PHIP, DGKI, and ZMYM4) are linked to severe childhood obesity • Wild-type PHIP enhances POMC transcription, but variants in PHIP repress POMC • Rare variants in BMI-associated loci from GWAS are enriched in severe obesity • Genetic architecture of severe childhood obesity reveals a continuum of causality, Childhood obesity can be caused by penetrant mutations in a number of genes controlling appetite and body weight. Marenne et al. identify three genes with mutations with variable penetrance in a continuum of causality in childhood obesity, and demonstrate that variants in PHIP repress POMC transcription.
Published: 2020

4. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author: Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjornsson, Gardar, Fatemifar, Ghazaleh, Hedman, Asa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Arnlov, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Doerr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engstrom, Gunnar, Esko, Tonu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Gudbjartsson, Daniel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Kober, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, Maerz, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, Stott, David J, Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G, Veluchamy, Abirami, Voelker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Waterworth, Dawn, Weeke, Peter E, Weiss, Raul, Wiggins, Kerri L, Xing, Heming, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J, McMurray, John JV, Yang, Jian, Visscher, Peter M, Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A, Sattar, Naveed, Holmes, Michael V, Cappola, Thomas P, Asselbergs, Folkert W, Hingorani, Aroon D, Kuchenbaecker, Karoline, Ellinor, Patrick T, Lang, Chim C, Stefansson, Kari, Smith, J Gustav, Vasan, Ramachandran S, Swerdlow, Daniel I, Lumbers, R Thomas, Abecasis, Goncalo, Backman, Joshua, Bai, Xiaodong, Balasubramanian, Suganthi, Banerjee, Nilanjana, Baras, Aris, Barnard, Leland, Beechert, Christina, Blumenfeld, Andrew, Cantor, Michael, Chai, Yating, Coppola, Giovanni, Damask, Amy, Dewey, Frederick, Economides, Aris, Eom, Gisu, Forsythe, Caitlin, Fuller, Erin D, Gu, Zhenhua, Gurski, Lauren, Guzzardo, Paloma M, Habegger, Lukas, Hahn, Young, Hawes, Alicia, van Hout, Cristopher, Jones, Marcus B, Khalid, Shareef, Lattari, Michael, Li, Alexander, Lin, Nan, Liu, Daren, Lopez, Alexander, Manoochehri, Kia, Marchini, Jonathan, Marcketta, Anthony, Maxwell, Evan K, McCarthy, Shane, Mitnaul, Lyndon J, O'Dushlaine, Colm, Overton, John D, Padilla, Maria Sotiropoulos, Paulding, Charles, Penn, John, Pradhan, Manasi, Reid, Jeffrey G, Schleicher, Thomas D, Schurmann, Claudia, Shuldiner, Alan, Staples, Jeffrey C, Sun, Dylan, Toledo, Karina, Ulloa, Ricardo H, Widom, Louis, Wolf, Sarah E, Yadav, Ashish, Ye, Bin, Ctr, Regeneron Genetics, Shah, Sonia [0000-0001-5860-4526], Henry, Albert [0000-0001-7422-2288], Roselli, Carolina [0000-0001-5267-6756], Lin, Honghuang [0000-0003-3043-3942], Chaffin, Mark D. [0000-0002-1234-5562], Helgadottir, Anna [0000-0002-1806-2467], Verweij, Niek [0000-0002-4303-7685], Almgren, Peter [0000-0002-0473-0241], Chen, Xu [0000-0002-7299-3238], Ghanbari, Mohsen [0000-0002-9476-7143], Giedraitis, Vilmantas [0000-0003-3423-2021], Gross, Stefan [0000-0003-4121-7161], Guðbjartsson, Daníel F. [0000-0002-5222-9857], Hyde, Craig L. [0000-0002-6939-287X], Ingelsson, Erik [0000-0003-2256-6972], Jukema, J. Wouter [0000-0002-3246-8359], Kleber, Marcus E. [0000-0003-0663-7275], Koekemoer, Andrea [0000-0001-8222-3547], Langenberg, Claudia [0000-0002-5017-7344], Lindgren, Cecilia M. [0000-0002-4903-9374], Lovering, Ruth C. [0000-0002-9791-0064], Luan, Jian’an [0000-0003-3137-6337], Magnusson, Patrik [0000-0002-7315-7899], Mahajan, Anubha [0000-0001-5585-3420], Mordi, Ify R. [0000-0002-2686-729X], Morris, Andrew D. [0000-0002-1766-0473], Nagle, Michael W. [0000-0002-4677-7582], Nelson, Christopher P. [0000-0001-8025-2897], Palmer, Colin N. A. [0000-0002-6415-6560], Rice, Kenneth M. [0000-0002-3071-7278], Rotter, Jerome I. [0000-0001-7191-1723], Salomaa, Veikko [0000-0001-7563-5324], van Setten, Jessica [0000-0002-4934-7510], Svensson, Per [0000-0003-0372-6272], Taylor, Kent D. [0000-0002-2756-4370], Teder-Laving, Maris [0000-0002-5872-1850], Teumer, Alexander [0000-0002-8309-094X], Tyl, Benoit [0000-0001-5297-8412], Uitterlinden, Andre G. [0000-0002-7276-3387], Völker, Uwe [0000-0002-5689-3448], Wiggins, Kerri L. [0000-0003-2749-1279], Hemingway, Harry [0000-0003-2279-0624], Yang, Jian [0000-0003-2001-2474], Visscher, Peter M. [0000-0002-2143-8760], Lubitz, Steven A. [0000-0002-9599-4866], Sattar, Naveed [0000-0002-1604-2593], Cappola, Thomas P. [0000-0002-9630-7204], Asselbergs, Folkert W. [0000-0002-1692-8669], Kuchenbaecker, Karoline [0000-0001-9726-603X], Ellinor, Patrick T. [0000-0002-2067-0533], Vasan, Ramachandran S. [0000-0001-7357-5970], Lumbers, R. Thomas [0000-0002-9077-4741], Apollo - University of Cambridge Repository, Chaffin, Mark D [0000-0002-1234-5562], Guðbjartsson, Daníel F [0000-0002-5222-9857], Hyde, Craig L [0000-0002-6939-287X], Jukema, J Wouter [0000-0002-3246-8359], Kleber, Marcus E [0000-0003-0663-7275], Lindgren, Cecilia M [0000-0002-4903-9374], Lovering, Ruth C [0000-0002-9791-0064], Luan, Jian'an [0000-0003-3137-6337], Mordi, Ify R [0000-0002-2686-729X], Morris, Andrew D [0000-0002-1766-0473], Nagle, Michael W [0000-0002-4677-7582], Nelson, Christopher P [0000-0001-8025-2897], Palmer, Colin NA [0000-0002-6415-6560], Rice, Kenneth M [0000-0002-3071-7278], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Uitterlinden, Andre G [0000-0002-7276-3387], Wiggins, Kerri L [0000-0003-2749-1279], Visscher, Peter M [0000-0002-2143-8760], Lubitz, Steven A [0000-0002-9599-4866], Cappola, Thomas P [0000-0002-9630-7204], Asselbergs, Folkert W [0000-0002-1692-8669], Ellinor, Patrick T [0000-0002-2067-0533], Vasan, Ramachandran S [0000-0001-7357-5970], Lumbers, R Thomas [0000-0002-9077-4741], Palmer, Colin N A [0000-0002-6415-6560], Cardiovascular Centre (CVC), University of Queensland [Brisbane], University College of London [London] (UCL), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University Medical Center Groningen [Groningen] (UMCG), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), deCODE genetics [Reykjavik], Karolinska Institutet [Stockholm], Pfizer, University of Pennsylvania [Philadelphia], University of Groningen [Groningen], Imperial College London, Lund University [Lund], Herlev and Gentofte Hospital, Massachusetts General Hospital [Boston], Department of Neurobiology, Care Sciences and Society [Stockholm, Sweden] (Division of Family Medicine), Dalarna University, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, Department of Biostatistics, University of Washington [Seattle], Emory University School of Medicine, Emory University [Atlanta, GA], The University of Texas Medical School at Houston, Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, Novartis Institutes for BioMedical Research (NIBR), University of Liverpool, Universität Heidelberg [Heidelberg], Medizinische Fakultät Mannheim, The Alan Turing Institute, Ninewells Hospital and Medical School [Dundee], Universität Greifswald - University of Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Minnesota System, Regeneron Pharmaceuticals [Tarrytown], Department of Clinical Sciences, Cardiovascular Epidemiology, Skane University Hospital [Lund], Institute of Genomics [Tartu, Estonia], University of Tartu, Robertson Centre for Biostatistics, University of Glasgow, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Uppsala University, Brigham & Women’s Hospital [Boston] (BWH), University of Maryland School of Medicine, University of Maryland System, School of Science and Engineering (Reykjavik University), Carver College of Medicine, University of Iowa, Geisinger Health System [Danville, PA, USA], Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford Cardiovascular Institute, Uppsala Universitet [Uppsala], Leiden University Medical Center (LUMC), Einthoven Laboratory for Experimental Vascular Medicine (ELEVM - LEIDEN), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Glenfield Hospital, University Hospitals Leicester, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Big Data Institute, University of Oxford [Oxford], University of Iowa [Iowa City], The Wellcome Trust Centre for Human Genetics [Oxford], Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Medical University Graz, Skane University Hospital [Malmo], Vanderbilt University School of Medicine [Nashville], University of Edinburgh, Université médicale de Vienne, Autriche, National Institute for Health and Welfare [Helsinki], University of Turku, Birmingham Women's and Children's NHS Foundation Trust, Kaiser Permanente, Harbor UCLA Medical Center [Torrance, Ca.], Los Angeles Biomedical Research Institute (LA BioMed), University Medical Center [Utrecht], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Seattle Epidemiologic Research and Information Center [Seattle], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Department of Cardiology, Södersjukhuset, Stockholm, Estonian Genome and Medicine, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Aalborg University [Denmark] (AAU), Institut de Recherches SERVIER (IRS), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, GlaxoSmithKline, Glaxo Smith Kline, Northeastern Ohio Medical University (NEOMED), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Department of Cardiovascular Sciences [Leicester], University of Leicester, Queensland Brain Institute, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, University of Dundee, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Atherosclerosis Risk in Communities Study (ARIC)The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC- 55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694 and RC2 HL102419, National Human Genome Research Institute contract U01HG004402, and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT- CHF)This project was funded by a grant from the European Commission (FP7‐242209‐ BIOSTAT‐CHF, EudraCT 2010–020808–29). Cardiovascular Health Study (CHS) This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Heart Failure Study (deCODE) We at deCODE thank the women and men of Iceland that have participated in our studies and our colleagues that contributed to data collection and processing. DiscovEHR We acknowledge and thank all participants in Geisinger’s MyCode Community Health Initiative for their support and permission to use their health and genomic information in the DiscovEHR collaboration. This work was supported by the Regeneron Genetics Center and Geisinger. Estonian Genome Center at the University of Tartu (EGCUT) This study was supported by Estonian Research Council Grant IUT20-60, EU, H2020 grant 692145, European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012) GENTRANSMED. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) The EPHESUS was supported by Pfizer, Inc. The European Prospective Investigation of Cancer, Norfolk study (EPIC-Norfolk) The EPIC-Norfolk Study is supported by programme grants from the Medical Research Council UK (G1000143) and Cancer Research UK (C864/A14136) and with additional support from the European Union, Stroke Association, British Heart Foundation, Research into Ageing, Department of Health, The Wellcome Trust and the Food Standards Agency. NJW and CL also acknowledge support from the Medical Research Council, UK (MC_UU_12015/1, MC_PC_13048). We thank all EPIC participants and staff for their contribution to the study, and thank staff from the Technical, Field Epidemiology and Data Functional Group Teams of the Medical Research Council Epidemiology Unit in Cambridge, UK, for carrying out sample preparation, DNA provision and quality control, genotyping and data handling work. Framingham Heart Study (FHS) This work was conducted using data and resources from the Framingham Heart Study (FHS) of the National Heart Lung and Blood Institute and Boston University School of Medicine. The study was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC-25195 and HHSN268201500001I) and its contract with Affymetrix, Inc for genotyping services (Contract No.N02-HL-6-4278). The work was also supported by R01 HL093328, R01 HL105993, and R01 HL71039 (PI: Ramachandran). FINRISK V.S. has been supported by the Finnish Foundation for Cardiovascular Research. Genetics of Diabetes Audit and Research Tayside Scotland GoDARTS) The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (supporting GoDARTS) was funded by the Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT programme. We acknowledge the support of the Health Informatics Centre, University of Dundee, for managing and supplying the anonymized data and NHS Tayside, the original data owner. The Genetic Risk Assessment of Defibrillator Events (GRADE) NIH-NHLBI R01 HL77398 (Genetic Modulators of Sudden Death). S.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study We extend our appreciation to the participants of the LURIC study, without their collaboration, this article would not have been written. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg and Ulm, Germany. LURIC has received funding from the 7th Framework Program (RiskyCAD, grant agreement number 305739 and Atheroremo, grant agreement number 201668) of the European Union. Malmö Diet and Cancer Study (MDCS) J. Gustav Smith was supported by grants from the Swedish Heart-Lung Foundation (2016- 0134 and 2016-0315), the Swedish Research Council (2017-02554), the European Research Council (ERC-STG-2015-679242), the Crafoord Foundation, Skåne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349-2006-237, Strategic Research Area Exodiab Dnr 2009-1039) and Swedish Foundation for Strategic Research (Dnr IRC15- 0067) to the Lund University Diabetes Center. The Malmo Diet and Cancer Study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, and the Malmo city council. Penn Heart Failure Study (PHFS) The study was supported by NIH grants (NIH R01L088577 and NIH R01H105993). Prevention of REnal and Vascular ENd-stage Disease (PREVEND) The Prevention of Renal and Vascular Endstage Disease Study (PREVEND) genetics is supported by the Dutch Kidney Foundation (Grant E033), the EU project grant GENECURE (FP-6 LSHM CT 2006 037697), the National Institutes of Health (grant LM010098), the Netherlands organisation for health research and development (NWO VENI grant 916.761.70), and the Dutch Inter University Cardiology Institute Netherlands (ICIN). Niek Verweij was supported by NWO VENI grant 016.186.125. PROspective Study of Pravastatin in the Elderly at Risk for vascular disease (PROSPER)The PROSPER study was supported by an investigator-initiated grant obtained from Bristol- Myers Squibb. Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Study of Health in Pomerania (SHIP) SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID)SOLID-TIMI 52 was funded by GlaxoSmithKline. TwinGene (TwinGene) TwinGene received funding from the Swedish Research Council (M-2005-1112), GenomEUtwin (EU/QLRT-2001-01254, QLG2-CT-2002-01254), NIH DK U01-066134, The Swedish Foundation for Strategic Research (SSF) and the Heart and Lung foundation no. 20070481. TwinGene is part of the Swedish Twin Registry which is managed by Karolinska Institutet and receives funding through the Swedish Research Council (2017–00641). UK Biobank (UKBiobank) This research has been conducted using the UK Biobank Resource under Application Number 15422. This work was supported in part by grants to R.T.L. from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074, MRC Proximity to Discovery Award Scheme, the American Heart Association Institute for Precision Mecidine, Pfizer Ltd, the University College London British Heart Foundation Research Accelerator (AA/18/6/34223), and was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A. H. is supported by the British Heart Foundation Cardiovascular Biomedicine PhD studentship. R.T.L is supported by a UK Research and Innovation Rutherford Fellowship and was previously supported by a National Institutes of Health Research Clinical Lectureship. Uppsala Longitudinal Study of Adult Men (ULSAM) J.Ä. is supported by the Swedish Research Council and the Swedish Heart Lung foundation. C.M.L is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138- 27). Women’s Genome Health Study (WGHS) The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467, HL099355) and the National Cancer Institute (CA047988 and UM1CA182913), with collaborative scientific support and funding for genotyping provided by Amgen., Epidemiology, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: 0301 basic medicine, Dánartíðni, Epidemiology, LOCI, 45/43, General Physics and Astronomy, Muscle Proteins, Genome-wide association study, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Bioinformatics, Genome-wide association studies, DISEASE, Ventricular Function, Left, Coronary artery disease, 0302 clinical medicine, Risk Factors, Atrial Fibrillation, IMPUTATION, Medicine, Blóðrásarsjúkdómar, 692/308/174, lcsh:Science, 2. Zero hunger, RISK, Multidisciplinary, Microfilament Proteins, article, Atrial fibrillation, Mendelian Randomization Analysis, CATALOG, 3. Good health, OBESITY, Erfðarannsóknir, Cardiomyopathies, Medical Genetics, Cyclin-Dependent Kinase Inhibitor p21, Science, 631/208/205/2138, Heart failure, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 631/443/592/2727, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, RESOURCE, Humans, Mortality, METAANALYSIS, Genetic association, Medicinsk genetik, Adaptor Proteins, Signal Transducing, Heart Failure, HYPERTENSION, business.industry, Case-control study, Klinisk medicin, 692/699/75/230, General Chemistry, Cardiovascular genetics, medicine.disease, R1, 030104 developmental biology, Case-Control Studies, lcsh:Q, Morbidity, Clinical Medicine, business, Apoptosis Regulatory Proteins, Carrier Proteins, Genome-Wide Association Study
Abstract: Publisher's version (útgefin grein), Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies., We acknowledge the contribution from the EchoGen Consortium.
Published: 2020

5. Associations of autozygosity with a broad range of human phenotypes

Author: Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. B., Wijmenga, C., Wong, T. -Y., Wright, J., Yang, J., Yu, L., Zemel, B. S., Zonderman, A. B., Perola, M., Magnusson, P. K. E., Uitterlinden, A. G., Kooner, J. S., Chasman, D. I., Loos, R. J. F., Franceschini, N., Franke, L., Haley, C. S., Hayward, C., Walters, R. G., Perry, J. R. B., Esko, T., Helgason, A., Stefansson, K., Joshi, P. K., Kubo, M., Wilson, J. F., Læknadeild (HÍ), Faculty of Medicine (UI), Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ), Faculty of Sociology, Anthropology and Folkloristics (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), School of Engineering and Natural Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), Félagsvísindasvið (HÍ), School of Social Sciences (UI), Háskóli Íslands, University of Iceland, Clark, David W [0000-0002-1025-9185], Okada, Yukinori [0000-0002-0311-8472], Moore, Kristjan H S [0000-0002-9579-4362], Mason, Dan [0000-0002-0026-9216], Pirastu, Nicola [0000-0002-5363-3886], Gandin, Ilaria [0000-0003-3196-2491], Deelen, Patrick [0000-0002-5654-3966], Schurmann, Claudia [0000-0003-4158-9192], Medina-Gomez, Carolina [0000-0001-7999-5538], Karlsson, Robert [0000-0002-8949-2587], Bao, Yanchun [0000-0002-6102-5098], Biino, Ginevra [0000-0002-9936-946X], Brumat, Marco [0000-0003-3268-039X], Chai, Jin-Fang [0000-0003-3770-1137], Eccles, David A [0000-0003-4634-4995], Gordon, Scott 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C. [0000-0001-5564-301X], Porteous, David J [0000-0003-1249-6106], Rioux, John D [0000-0001-7560-8326], Rivadeneira, Fernando [0000-0001-9435-9441], Rotimi, Charles [0000-0001-5759-053X], Rotter, Jerome I [0000-0001-7191-1723], Rudan, Igor [0000-0001-6993-6884], Sattar, Naveed [0000-0002-1604-2593], Sim, Xueling [0000-0002-1233-7642], Smith, Jennifer A [0000-0002-3575-5468], Teumer, Alexander [0000-0002-8309-094X], Timpson, Nicholas J [0000-0002-7141-9189], Tuomi, Tiinamaija [0000-0002-8306-6202], Wang, Carol A [0000-0002-4301-3974], Weir, David R [0000-0002-1661-2402], Whitfield, John B [0000-0002-1103-0876], Magnusson, Patrik K. E. [0000-0002-7315-7899], Uitterlinden, André G [0000-0002-7276-3387], Loos, Ruth J. F. [0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics
Subjects: 0301 basic medicine, 631/208/1397, Chemistry(all), Health Status, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, MESH: Haplotype, MESH: Cognition, 030105 genetics & heredity, Runs of Homozygosity, Biochemistry, Consanguinity, Cognition, Inbreeding depression, 2.1 Biological and endogenous factors, Body Size, Inbreeding, Skyldleikarækt, Aetiology, Human phenotypes, lcsh:Science, MESH: Health Status, Genetics, Multidisciplinary, Inbreeding Depression, Confounding, Homozygote, RUNS, 631/208/205, 631/208/721, 3. Good health, genomic inbreeding coefficients, MESH: Risk-Taking, 631/208/730, Autozygosit, homozygosity, Erfðarannsóknir, Medical Genetics, genomic inbreeding coefficient, MESH: Homozygote, Offspring, Science, Autozygosity, Blóðsifjar, 610 Medicine & health, Biology, INBREEDING DEPRESSION, HOMOZYGOSITY, FERTILITY, QUANTIFICATION, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, Association, 03 medical and health sciences, Risk-Taking, 360 Social problems & social services, Journal Article, Humans, ddc:610, Allele, Alleles, Medicinsk genetik, Genetic association study, MESH: Consanguinity, MESH: Body Size, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), MESH: Alleles, Haplotype, MESH: Fertility, General Chemistry, Brain Disorders, MESH: Inbreeding Depression, 030104 developmental biology, Fertility, Haplotypes, Genetic markers, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, Genetics and Molecular Biology(all)
Abstract: Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.
Published: 2019

6. A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5)

Author: Tadej Battelino, J. Hans DeVries, Theis Gondolf, Mark L. Evans, David C. Klonoff, A. Hyseni, Eric Renard, Wendy Lane, Tina Graungaard, Hans-Peter Kempe, Mills Peninsula Medical Center, MRC Epidemiology Unit [Cambridge, UK] (Wellcome Trust-MRC Institute of Metabolic Science), University of Cambridge [UK] (CAM)-Addenbrooke’s Hospital [Cambridge, UK]-Wellcome Trust-MRC Institute of Metabolic Science (IMS), Mountain Diabetes and Endocrine Center, Centre for Diabetes and Nutrition Ludwigshafen, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Amsterdam UMC - Amsterdam University Medical Center, Profil Institute for Metabolic Research GmbH, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Novo nordisk pharma, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Nowak, Cécile, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Klonoff, David C [0000-0002-0624-698X], Renard, Eric [0000-0002-3407-7263], DeVries, J Hans [0000-0001-9196-9906], Battelino, Tadej [0000-0002-0273-4732], Apollo - University of Cambridge Repository, Endocrinology, and AGEM - Endocrinology, metabolism and nutrition
Subjects: Adult, Male, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Rate ratio, Infusions, Subcutaneous, Gastroenterology, Insulin aspart, Excipients, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin Infusion Systems, Double-Blind Method, Internal medicine, Statistical significance, Internal Medicine, medicine, Clinical endpoint, Humans, Hypoglycemic Agents, Insulin Aspart, Dosage Forms, Glycated Hemoglobin, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Type 1 diabetes, business.industry, CSII, Original Articles, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Confidence interval, Hypoglycemia, 3. Good health, Discontinuation, Clinical trial, Postprandial, Diabetes Mellitus, Type 1, Insulin therapy, Original Article, Female, business, medicine.drug
Abstract: International audience; Aim: To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) vs insulin aspart (IAsp) used in continuous subcutaneous insulin infusion (CSII) in participants with type 1 diabetes (T1D).Materials and methods: This was a double-blind, treat-to-target, randomized, 16-week trial investigating CSII treatment with faster aspart (n = 236) or IAsp (n = 236). All available information, regardless of treatment discontinuation, was used for the evaluation of effect.Results: Faster aspart was non-inferior to IAsp regarding the change from baseline in glycated haemoglobin (HbA1c; primary endpoint). The mean HbA1c changed from 58.4 mmol/mol (7.5%) at baseline to 57.8 mmol/mol (7.4%) with faster aspart and to 56.8 mmol/mol (7.4%) with IAsp after 16 weeks' treatment, with an estimated treatment difference (ETD) of 1.0 mmol/mol (95% confidence interval [CI] 0.14; 1.87) or 0.09% (95% CI 0.01; 0.17; P < 0.001) for non-inferiority (0.4% margin; P < 0.02 for statistical significance in favour of IAsp). Faster aspart was superior to IAsp in change from baseline in 1-hour postprandial glucose (PPG) increment after a meal test (ETD -0.91 mmol/L [95% CI -1.43; -0.39] or -16.4 mg/dL [95% CI -25.7; -7.0]; P = 0.001), with statistically significant reductions also at 30 minutes and 2 hours. The improvement in PPG was reflected in the change from baseline in 1-hour interstitial glucose increment after all meals (ETD -0.21 mmol/L [95% CI -0.31; -0.11] or -3.77 mg/dL [95% CI -5.53; -2.01]). There was no statistically significant difference in the overall rate of severe or blood glucose-confirmed hypoglycaemia (estimated rate ratio 1.00 [95% CI 0.85; 1.16]). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and 4-week run-in periods (4 vs 0).Conclusions: Faster aspart provides an effective and safe option for CSII treatment in T1D.
Published: 2018

7. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author: Symen Ligthart, Ahmad Vaez, Urmo Võsa, Maria G. Stathopoulou, Paul S. de Vries, Bram P. Prins, Peter J. Van der Most, Toshiko Tanaka, Elnaz Naderi, Lynda M. Rose, Ying Wu, Robert Karlsson, Maja Barbalic, Honghuang Lin, René Pool, Gu Zhu, Aurélien Macé, Carlo Sidore, Stella Trompet, Massimo Mangino, Maria Sabater-Lleal, John P. Kemp, Ali Abbasi, Tim Kacprowski, Niek Verweij, Albert V. Smith, Tao Huang, Carola Marzi, Mary F. Feitosa, Kurt K. Lohman, Marcus E. Kleber, Yuri Milaneschi, Christian Mueller, Mahmudul Huq, Efthymia Vlachopoulou, Leo-Pekka Lyytikäinen, Christopher Oldmeadow, Joris Deelen, Markus Perola, Jing Hua Zhao, Bjarke Feenstra, Marzyeh Amini, Jari Lahti, Katharina E. Schraut, Myriam Fornage, Bhoom Suktitipat, Wei-Min Chen, Xiaohui Li, Teresa Nutile, Giovanni Malerba, Jian’an Luan, Tom Bak, Nicholas Schork, Fabiola Del Greco M., Elisabeth Thiering, Anubha Mahajan, Riccardo E. Marioni, Evelin Mihailov, Joel Eriksson, Ayse Bilge Ozel, Weihua Zhang, Maria Nethander, Yu-Ching Cheng, Stella Aslibekyan, Wei Ang, Ilaria Gandin, Loïc Yengo, Laura Portas, Charles Kooperberg, Edith Hofer, Kumar B. Rajan, Claudia Schurmann, Wouter den Hollander, Tarunveer S. Ahluwalia, Jing Zhao, Harmen H.M. Draisma, Ian Ford, Nicholas Timpson, Alexander Teumer, Hongyan Huang, Simone Wahl, YongMei Liu, Jie Huang, Hae-Won Uh, Frank Geller, Peter K. Joshi, Lisa R. Yanek, Elisabetta Trabetti, Benjamin Lehne, Diego Vozzi, Marie Verbanck, Ginevra Biino, Yasaman Saba, Ingrid Meulenbelt, Jeff R. O’Connell, Markku Laakso, Franco Giulianini, Patrik K.E. Magnusson, Christie M. Ballantyne, Jouke Jan Hottenga, Grant W. Montgomery, Fernando Rivadineira, Rico Rueedi, Maristella Steri, Karl-Heinz Herzig, David J. Stott, Cristina Menni, Mattias Frånberg, Beate St. Pourcain, Stephan B. Felix, Tune H. Pers, Stephan J.L. Bakker, Peter Kraft, Annette Peters, Dhananjay Vaidya, Graciela Delgado, Johannes H. Smit, Vera Großmann, Juha Sinisalo, Ilkka Seppälä, Stephen R. Williams, Elizabeth G. Holliday, Matthijs Moed, Claudia Langenberg, Katri Räikkönen, Jingzhong Ding, Harry Campbell, Michele M. Sale, Yii-Der I. Chen, Alan L. James, Daniela Ruggiero, Nicole Soranzo, Catharina A. Hartman, Erin N. Smith, Gerald S. Berenson, Christian Fuchsberger, Dena Hernandez, Carla M.T. Tiesler, Vilmantas Giedraitis, David Liewald, Krista Fischer, Dan Mellström, Anders Larsson, Yunmei Wang, William R. Scott, Matthias Lorentzon, John Beilby, Kathleen A. Ryan, Craig E. Pennell, Dragana Vuckovic, Beverly Balkau, Maria Pina Concas, Reinhold Schmidt, Carlos F. Mendes de Leon, Erwin P. Bottinger, Margreet Kloppenburg, Lavinia Paternoster, Michael Boehnke, A.W. Musk, Gonneke Willemsen, David M. Evans, Pamela A.F. Madden, Mika Kähönen, Zoltán Kutalik, Magdalena Zoledziewska, Ville Karhunen, Stephen B. Kritchevsky, Naveed Sattar, Genevieve Lachance, Robert Clarke, Tamara B. Harris, Olli T. Raitakari, John R. Attia, Diana van Heemst, Eero Kajantie, Rossella Sorice, Giovanni Gambaro, Robert A. Scott, Andrew A. Hicks, Luigi Ferrucci, Marie Standl, Cecilia M. Lindgren, John M. Starr, Magnus Karlsson, Lars Lind, Jun Z. Li, John C. Chambers, Trevor A. Mori, Eco J.C.N. de Geus, Andrew C. Heath, Nicholas G. Martin, Juha Auvinen, Brendan M. Buckley, Anton J.M. de Craen, Melanie Waldenberger, Konstantin Strauch, Thomas Meitinger, Rodney J. Scott, Mark McEvoy, Marian Beekman, Cristina Bombieri, Paul M. Ridker, Karen L. Mohlke, Nancy L. Pedersen, Alanna C. Morrison, Dorret I. Boomsma, John B. Whitfield, David P. Strachan, Albert Hofman, Peter Vollenweider, Francesco Cucca, Marjo-Riitta Jarvelin, J. Wouter Jukema, Tim D. Spector, Anders Hamsten, Tanja Zeller, André G. Uitterlinden, Matthias Nauck, Vilmundur Gudnason, Lu Qi, Harald Grallert, Ingrid B. Borecki, Jerome I. Rotter, Winfried März, Philipp S. Wild, Marja-Liisa Lokki, Michael Boyle, Veikko Salomaa, Mads Melbye, Johan G. Eriksson, James F. Wilson, Brenda W.J.H. Penninx, Diane M. Becker, Bradford B. Worrall, Greg Gibson, Ronald M. Krauss, Marina Ciullo, Gianluigi Zaza, Nicholas J. Wareham, Albertine J. Oldehinkel, Lyle J. Palmer, Sarah S. Murray, Peter P. Pramstaller, Stefania Bandinelli, Joachim Heinrich, Erik Ingelsson, Ian J. Deary, Reedik Mägi, Liesbeth Vandenput, Pim van der Harst, Karl C. Desch, Jaspal S. Kooner, Claes Ohlsson, Caroline Hayward, Terho Lehtimäki, Alan R. Shuldiner, Donna K. Arnett, Lawrence J. Beilin, Antonietta Robino, Philippe Froguel, Mario Pirastu, Tine Jess, Wolfgang Koenig, Ruth J.F. Loos, Denis A. Evans, Helena Schmidt, George Davey Smith, P. Eline Slagboom, Gudny Eiriksdottir, Andrew P. Morris, Bruce M. Psaty, Russell P. Tracy, Ilja M. Nolte, Eric Boerwinkle, Sophie Visvikis-Siest, Alex P. Reiner, Myron Gross, Joshua C. Bis, Lude Franke, Oscar H. Franco, Emelia J. Benjamin, Daniel I. Chasman, Josée Dupuis, Harold Snieder, Abbas Dehghan, Behrooz Z. Alizadeh, H. Marike Boezen, Gerjan Navis, Marianne Rots, Morris Swertz, Bruce H.R. Wolffenbuttel, Cisca Wijmenga, Emelia Benjamin, Tarunveer Singh Ahluwalia, James Meigs, Russell Tracy, Josh Bis, Nathan Pankratz, Alex Rainer, James G. Wilson, Josee Dupuis, Bram Prins, Urmo Vaso, Maria Stathopoulou, Terho Lehtimaki, Yalda Jamshidi, Sophie Siest, Andre G. Uitterlinden, Mohammadreza Abdollahi, Renate Schnabel, Ursula M. Schick, Aldi Kraja, Yi-Hsiang Hsu, Daniel S. Tylee, Alyson Zwicker, Rudolf Uher, George Davey-Smith, Andrew Hicks, Cornelia M. van Duijn, Cavin Ward-Caviness, J. Rotter, Ken Rice, Leslie Lange, Eco de Geus, Kari Matti Makela, David Stacey, Johan Eriksson, Tim M. Frayling, Eline P. Slagboom, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University Medical Center Groningen [Groningen] (UMCG), University of Isfahan, University of Tartu, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The University of Texas Health Science Center at Houston (UTHealth), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Split, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Process & Energy Laboratory, Delft University of Technology (TU Delft), Grand Lyon : communauté urbaine de Lyon, Interuniversity Cardiology Institute Netherlands, Department of Twin Research and Genetic Epidemiology, King's College London, London, Huazhong University of Science and Technology [Wuhan] (HUST), Division of Statistical Genomics, Washington University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Institut fuer Theoretische Physik (Institut fuer Theoretische Physik), Universität Heidelberg [Heidelberg] = Heidelberg University, Molecular Epidemiology, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Mahidol University [Bangkok], Northwest A and F University, Laboratoire d'Optimisation des Systèmes Industriels (LOSI), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS), Institute of Genetics and Biophysics, CNR, Naples, Università degli studi di Verona = University of Verona (UNIVR), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], University of Maryland School of Medicine, University of Maryland System, Institut National de l'Environnement Industriel et des Risques (INERIS), Institute of Pop. Genetics, CNR, Sassari, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, IT University of Copenhagen (ITU), Robertson Centre for Biostatistics, University of Glasgow, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, King‘s College London, Jinan University [Guangzhou], Institute of Oceanology [China], School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Shardna life science Pula Cagliari, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Medstar Research Institute, Department of Cardiology, Ernst-Moritz-Arndt University, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Department of Internal Medicine, University of Groningen and University Medical Center Groningen, Department of Epidemiology, Harvard School of Public Health, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Metacohorts Consortium, INEOS Technologies (SWITZERLAND), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, University of Edinburgh, School of Population Health [Crawley, Western Australia], The University of Western Australia (UWA), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), The Scripps Translational Science Institute and Scripps Health, Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, Centre for Population Health Sciences, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Luleå University of Technology (LUT), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Austrian Institute of Technology [Vienna] (AIT), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC), Department of Rheumatology and Clinical Epidemiology [Leiden University Medical Center] (LUMC), Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden-Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Virginia, Tampere University Hospital, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Department of Pathological Biochemistry, Royal Infirmary, Oxford University, University of Oxford, University of Newcastle [Callaghan, Australia] (UoN), Department of neurology, Institute of Metabolic Science, MRC, The Wellcome Trust Centre for Human Genetics [Oxford], Uppsala Universitet [Uppsala], QIMR Berghofer Medical Research Institute, Institute of Genetic Epidemiology [Neuherberg, Germany], Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Schizophrenia Research Institute [Sydney], Department of Genetics, University of North Carolina System (UNC)-University of North Carolina System (UNC), Vrije Universiteit Brussel (VUB), Population Health Sciences and Education, St George's University of London, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Health Sciences and Biocenter Oulu, University of Oulu, Medizinische Klinik und Poliklinik, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institute of Clinical Chemistry and Laboratory Medicine, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Departments of Epidemiology and Nutrition, Institute of Epidemiology [Neuherberg] (EPI), Medical University Graz, Transplantation Laboratory [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], CLinical Psychology, Genetics and Pathology, Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Center For Narcolepsy, Stanford University, Centre for Bone and Arthritis Research, University of Gothenburg (GU)-Institute of Medicine, MRC Human Gentics Unit, Inst Genet and Mol Med, Western General Hospital, Edinburgh, University of Maryland School of Medicine [Baltimore, MD, USA], Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Stockholm], Stockholm University, University of Bristol [Bristol], Universiteit Leiden, Department of Epidemiology, University of Washington, University of Washington [Seattle], Department of Epidemiology [Rotterdam], University of Groningen [Groningen], Dutch Initiative on Crohn and Colitis (ICC), Icelandic Heart Association [Kopavogur, Iceland] (IHA), Department of Physiology and Biophysics [Jackson, MS, USA], University of Southern Mississippi (USM), Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Department of Social Medicine, School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Medicine [Aurora, CO, USA], University of Colorado [Denver], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Mathematical Institute [Oxford] (MI), Institute of Psychiatry, Psychology & Neuroscience, King's College London, LifeLines Cohort Study, CHARGE Inflammation Working Group, Ligthart, S., Vaez, A., Vosa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., Van der Most, P. J., Tanaka, T., Naderi, E., Rose, L. M., Wu, Y., Karlsson, R., Barbalic, M., Lin, H., Pool, R., Zhu, G., Mace, A., Sidore, C., Trompet, S., Mangino, M., Sabater-Lleal, M., Kemp, J. P., Abbasi, A., Kacprowski, T., Verweij, N., Smith, A. V., Huang, T., Marzi, C., Feitosa, M. F., Lohman, K. K., Kleber, M. E., Milaneschi, Y., Mueller, C., Huq, M., Vlachopoulou, E., Lyytikainen, L. -P., Oldmeadow, C., Deelen, J., Perola, M., Zhao, J. H., Feenstra, B., Alizadeh, B. Z., Boezen, H. M., Franke, L., van der Harst, P., Navis, G., Rots, M., Snieder, H., Swertz, M., Wolffenbuttel, B. H. R., Wijmenga, C., Amini, M., Benjamin, E., Chasman, D. I., Dehghan, A., Ahluwalia, T. S., Meigs, J., Tracy, R., Bis, J., Eiriksdottir, G., Pankratz, N., Gross, M., Rainer, A., Wilson, J. G., Psaty, B. M., Dupuis, J., Prins, B., Vaso, U., Stathopoulou, M., Lehtimaki, T., Koenig, W., Jamshidi, Y., Siest, S., Uitterlinden, A. G., Abdollahi, M., Schnabel, R., Schick, U. M., Nolte, I. M., Kraja, A., Hsu, Y. -H., Tylee, D. S., Zwicker, A., Uher, R., Davey-Smith, G., Morrison, A. C., Hicks, A., van Duijn, C. M., Ward-Caviness, C., Boerwinkle, E., Rotter, J., Rice, K., Lange, L., de Geus, E., Morris, A. P., Makela, K. M., Stacey, D., Eriksson, J., Frayling, T. M., Slagboom, E. P., Lahti, J., Schraut, K. E., Fornage, M., Suktitipat, B., Chen, W. -M., Li, X., Nutile, T., Malerba, G., Luan, J., Bak, T., Schork, N., Del Greco, M. F., Thiering, E., Mahajan, A., Marioni, R. E., Mihailov, E., Ozel, A. B., Zhang, W., Nethander, M., Cheng, Y. -C., Aslibekyan, S., Ang, W., Gandin, I., Yengo, L., Portas, L., Kooperberg, C., Hofer, E., Rajan, K. B., Schurmann, C., den Hollander, W., Zhao, J., Draisma, H. H. M., Ford, I., Timpson, N., Teumer, A., Huang, H., Wahl, S., Liu, Y., Huang, J., Uh, H. -W., Geller, F., Joshi, P. K., Yanek, L. R., Trabetti, E., Lehne, B., Vozzi, D., Verbanck, M., Biino, G., Saba, Y., Meulenbelt, I., O'Connell, J. R., Laakso, M., Giulianini, F., Magnusson, P. K. E., Ballantyne, C. M., Hottenga, J. J., Montgomery, G. W., Rivadineira, F., Rueedi, R., Steri, M., Herzig, K. -H., Stott, D. J., Menni, C., Franberg, M., S, t. Pourcain B., Felix, S. B., Pers, T. H., Bakker, S. J. L., Kraft, P., Peters, A., Vaidya, D., Delgado, G., Smit, J. H., Grossmann, V., Sinisalo, J., Seppala, I., Williams, S. R., Holliday, E. G., Moed, M., Langenberg, C., Raikkonen, K., Ding, J., Campbell, H., Sale, M. M., Chen, Y. -D. I., James, A. L., Ruggiero, D., Soranzo, N., Hartman, C. A., Smith, E. N., Berenson, G. S., Fuchsberger, C., Hernandez, D., Tiesler, C. M. T., Giedraitis, V., Liewald, D., Fischer, K., Mellstrom, D., Larsson, A., Wang, Y., Scott, W. R., Lorentzon, M., Beilby, J., Ryan, K. A., Pennell, C. E., Vuckovic, D., Balkau, B., Concas, M. P., Schmidt, R., Mendes de Leon, C. F., Bottinger, E. P., Kloppenburg, M., Paternoster, L., Boehnke, M., Musk, A. W., Willemsen, G., Evans, D. M., Madden, P. A. F., Kahonen, M., Kutalik, Z., Zoledziewska, M., Karhunen, V., Kritchevsky, S. B., Sattar, N., Lachance, G., Clarke, R., Harris, T. B., Raitakari, O. T., Attia, J. R., van Heemst, D., Kajantie, E., Sorice, R., Gambaro, G., Scott, R. A., Hicks, A. A., Ferrucci, L., Standl, M., Lindgren, C. M., Starr, J. M., Karlsson, M., Lind, L., Li, J. Z., Chambers, J. C., Mori, T. A., de Geus, E. J. C. N., Heath, A. C., Martin, N. G., Auvinen, J., Buckley, B. M., de Craen, A. J. M., Waldenberger, M., Strauch, K., Meitinger, T., Scott, R. J., Mcevoy, M., Beekman, M., Bombieri, C., Ridker, P. M., Mohlke, K. L., Pedersen, N. L., Boomsma, D. I., Whitfield, J. B., Strachan, D. P., Hofman, A., Vollenweider, P., Cucca, F., Jarvelin, M. -R., Jukema, J. W., Spector, T. D., Hamsten, A., Zeller, T., Nauck, M., Gudnason, V., Qi, L., Grallert, H., Borecki, I. B., Rotter, J. I., Marz, W., Wild, P. S., Lokki, M. -L., Boyle, M., Salomaa, V., Melbye, M., Eriksson, J. G., Wilson, J. F., Penninx, B. W. J. H., Becker, D. M., Worrall, B. B., Gibson, G., Krauss, R. M., Ciullo, M., Zaza, G., Wareham, N. J., Oldehinkel, A. J., Palmer, L. J., Murray, S. S., Pramstaller, P. P., Bandinelli, S., Heinrich, J., Ingelsson, E., Deary, I. J., Magi, R., Vandenput, L., Desch, K. C., Kooner, J. S., Ohlsson, C., Hayward, C., Shuldiner, A. R., Arnett, D. K., Beilin, L. J., Robino, A., Froguel, P., Pirastu, M., Jess, T., Loos, R. J. F., Evans, D. A., Schmidt, H., Slagboom, P. E., Tracy, R. P., Visvikis-Siest, S., Reiner, A. P., Bis, J. C., Franco, O. H., Benjamin, E. J., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Epidemiology, Internal Medicine, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), VU University medical center, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, APH - Digital Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Universität Heidelberg [Heidelberg], University of Verona (UNIVR), Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IT University of Copenhagen, Technical University of Denmark [Lyngby] (DTU), Consiglio Nazionale delle Ricerche (CNR), University of Virginia [Charlottesville], Université de Lausanne (UNIL), University of Oxford [Oxford], University of Newcastle [Australia] (UoN), Centre d'économie industrielle i3 (CERNA i3), Centre National de la Recherche Scientifique (CNRS)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Helmholtz-Zentrum München (HZM), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Universitätsmedizin der Johannes-Gutenberg Universität Mainz, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Cardiff University-Medical Research Council, University of California-University of California, and DE CARVALHO, Philippe
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), Bipolar Disorder, LD SCORE REGRESSION, [SDV]Life Sciences [q-bio], Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Body Mass Index, inflammatory disorder, 80 and over, WIDE ASSOCIATION, EPIDEMIOLOGY, ta318, International HapMap Project, Child, Genetics (clinical), 2. Zero hunger, Genetics, Genetics & Heredity, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, C-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biology, system biology, DEPICT, Mendelian Randomization Analysis, 11 Medical And Health Sciences, Middle Aged, C-reactive protein, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, Mendelian randomization, schizophrenia, Adolescent, Adult, Aged, Biomarkers, C-Reactive Protein, Female, Genetic Loci, Genome-Wide Association Study, Humans, Inflammation, Liver, Metabolic Networks and Pathways, Schizophrenia, Young Adult, 3. Good health, [SDV] Life Sciences [q-bio], Medical genetics, Biomarker (medicine), Life Sciences & Biomedicine, Human, medicine.medical_specialty, CHARGE Inflammation Working Group, Biology, IMMUNITY, ta3111, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, CORONARY-HEART-DISEASE, Mendelian Randomization Analysi, 1000 Genomes Project, METAANALYSIS, Genetic association, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, ta1184, Metabolic Networks and Pathway, Biomarker, INSTRUMENTS, 06 Biological Sciences, 030104 developmental biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, LifeLines Cohort Study
Abstract: International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
Published: 2018

8. Mediation and modification of genetic susceptibility to obesity by eating behaviors

Author: Ken K. Ong, Véronique Pelloux, Emma A.D. Clifton, Felix R. Day, Marie-Aline Charles, Soren Brage, Blandine de Lauzon-Guillain, Karine Clément, Nicholas J. Wareham, Yves Akoli Koudou, Nita G. Forouhi, Barbara Heude, Simon J. Griffin, Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MRC Epidemiology Unit [Cambridge, UK] (Wellcome Trust-MRC Institute of Metabolic Science), University of Cambridge [UK] (CAM)-Addenbrooke’s Hospital [Cambridge, UK]-Wellcome Trust-MRC Institute of Metabolic Science (IMS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), de Lauzon-Guillain, Blandine [0000-0001-5887-8842], Clifton, Emma Ad [0000-0002-1649-7248], Day, Felix R [0000-0003-3789-7651], Brage, Soren [0000-0002-1265-7355], Forouhi, Nita G [0000-0002-5041-248X], Griffin, Simon J [0000-0002-2157-4797], Wareham, Nicholas J [0000-0003-1422-2993], Charles, Marie-Aline [0000-0003-4025-4390], Heude, Barbara [0000-0002-1565-1629], Ong, Ken K [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and de Lauzon-Guillain, Blandine
Subjects: Gerontology, Male, Emotions, Medicine (miscellaneous), Appetite, Eating, 0302 clinical medicine, Cognition, Risk Factors, Surveys and Questionnaires, 030212 general & internal medicine, Body mass index, media_common, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, Self-control, Emotional eating, Middle Aged, Genetic risk score, 3. Good health, Female, medicine.symptom, Dieting, Clinical psychology, Adult, Mediation (statistics), media_common.quotation_subject, Population, 030209 endocrinology & metabolism, Hyperphagia, Article, Self-Control, 03 medical and health sciences, BMI, Sex Factors, Genetic predisposition, medicine, Genetics, Humans, Genetic Predisposition to Disease, Eating behavior, Obesity, education, business.industry, Feeding Behavior, medicine.disease, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Gene-Environment Interaction, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background: Many genetic variants show highly robust associations with body mass index (BMI). However, the mechanisms through which genetic susceptibility to obesity operates are not well understood. Potentially modifiable mechanisms, including eating behaviors, are of particular interest to public health.Objective: Here we explore whether eating behaviors mediate or modify genetic susceptibility to obesity.Design: Genetic risk scores for BMI (BMI-GRSs) were calculated for 3515 and 2154 adults in the Fenland and EDEN (Etude des determinants pre et postnatals de la sante et du developpement de l'enfant) population-based cohort studies, respectively. The eating behaviors-emotional eating, uncontrolled eating, and cognitive restraint-were measured through the use of a validated questionnaire. The mediating effect of each eating behavior on the association between the BMI-GRS and measured BMI was assessed by using the Sobel test. In addition, we tested for interactions between each eating behavior and the BMI-GRS on BMI.Results: The association between the BMI-GRS and BMI was mediated by both emotional eating (EDEN: P-Sobel = 0.01; Fenland: P-Sobel = 0.02) and uncontrolled eating (EDEN: P-Sobel = 0.04; Fenland: P-Sobel = 0.0006) in both sexes combined. Cognitive restraint did not mediate this association (P-Sobel > 0.10), except among EDEN women (P-Sobel = 0.0009). Cognitive restraint modified the relation between the BMI-GRS and BMI among men (EDEN: P-interaction = 0.0001; Fenland: P-interaction = 0.04) and Fenland women (P-interaction = 0.0004). By tertiles of cognitive restraint, the association between the BMI-GRS and BMI was strongest in the lowest tertile of cognitive restraint, and weakest in the highest tertile.Conclusions: Genetic susceptibility to obesity was partially mediated by the "appetitive" eating behavior traits (uncontrolled and emotional eating) and, in 3 of the 4 population groups studied, was modified by cognitive restraint. High levels of cognitive control over eating appear to attenuate the genetic susceptibility to obesity. Future research into interventions designed to support restraint may help to protect genetically susceptible individuals from weight gain.
Published: 2017

9. Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study

Author: Lesli H. Larsen, Marie Kunešová, Arne Astrup, Dominique Langin, Marleen A. van Baak, J. Alfredo Martínez, Susan A. Jebb, Wim H. M. Saris, Karani Santhanakrishnan Vimaleswaran, Andreas Pfeiffer, Claus Holst, Teodora Handjieva-Darlenska, Nathalie Viguerie, Angeliki Papadaki, Jorg Hager, Lars Ängquist, Thomas Larsen, Thorkild I. A. Sørensen, Ruth J. F. Loos, Department of Human Nutrition, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Institute of Preventive Medicine, Copenhagen University Hospitals, MRC Epidemiology Unit, Addenbrooke's Hospital-Institute of Metabolic Science, Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Metabolic Science, MRC, Department of Nutrition, Dietetics and Metabolic Diseases, National Transport Hospital, MRC Human Nutrition Research, Elsie Widdowson Laboratory, Institute of Endocrinology, Obesity Management Center, Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Department of Social Medicine, University of Crete [Heraklion] (UOC), Department of Endocrinology, Diabetes & Nutrition, German Institute of Human Nutrition-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht]-Maastricht University [Maastricht], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Simon, Marie Francoise, Humane Biologie, and RS: NUTRIM - R1 - Metabolic Syndrome
Subjects: Male, 030309 nutrition & dietetics, BEHAVIOR INTERACTIONS, MESH: Dietary Proteins, PROTEIN, Medicine (miscellaneous), MESH: Food Habits, Weight Gain, Body Mass Index, MESH: Genotype, 0302 clinical medicine, Weight loss, MESH: Obesity, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: DNA, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Glycemic index, OBESITY, MESH: Waist Circumference, MESH: Weight Gain, DIETS, Female, Dietary Proteins, Waist Circumference, medicine.symptom, Adult, medicine.medical_specialty, Waist, Genotype, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, LOSS MAINTENANCE, Biology, Polymorphism, Single Nucleotide, MESH: Genetic Loci, MESH: Body Mass Index, 03 medical and health sciences, MESH: Weight Loss, Internal medicine, Weight Loss, medicine, Humans, Caloric Restriction, Glycemic, MESH: Caloric Restriction, MESH: Humans, MESH: Adult, DNA, Feeding Behavior, medicine.disease, Obesity, MESH: Male, Endocrinology, Genetic Loci, MESH: Glycemic Index, GLYCEMIC INDEX, Body mass index, Weight gain, MESH: Female
Abstract: International audience; BACKGROUND: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. OBJECTIVE: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. DESIGN: In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. RESULTS: After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. CONCLUSION: The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.
Published: 2016

10. Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network

Author: Angela Pinot de Moira, Katrine Strandberg-Larsen, Tom Bishop, Marie Pedersen, Demetris Avraam, Tim Cadman, Lucinda Calas, Maribel Casas, Blandine de Lauzon Guillain, Ahmed Elhakeem, Ana Esplugues, Marisa Estarlich, Rachel E. Foong, Sido Haakma, Jennifer R. Harris, Rae-Chi Huang, Hazel Inskip, Aitana Lertxundi, Sara M. Mensink-Bout, Johanna L.T. Nader, Costanza Pizzi, Maja Popovic, Theodosia Salika, Jordi Sunyer, Evelien R. Van Meel, Morris A. Swertz, Vincent W.V. Jaddoe, Paul Burton, Liesbeth Duijts, Anne-Marie Nybo Andersen, Pediatrics, Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), University of Cambridge [UK] (CAM), Newcastle University [Newcastle], Bristol Medical School, University of Bristol [Bristol], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Erasmus University Medical Center [Rotterdam] (Erasmus MC), European Project: 733206,H2020,H2020-SC1-2016-RTD,LIFECYCLE(2017), Department of Public Health, University of Copenhagen, Copenhagen, Denmark, parent, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: FAIR (findableaccessibleinteroperableand reusable), Immunology, FAIR (findable, cat, ownership, allergic sensitization, Cat, accessible, allergic sensitisation, asthma, birth cohort, children, dog, exposure, interoperable and reusable), lifecourse epidemiology, meta-analysis, birth cohortlife course epidemiology, Cohort Studies, Dogs, interoperable, Odds Ratio, Animals, Humans, Immunology and Allergy, and reusable), Child, ComputingMilieux_MISCELLANEOUS, Environmental Exposure, Allergens, life course epidemiology, Child, Preschool, Cats, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Background: studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure.Objective: our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization.Methods: we used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis.Results: the prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization.Conclusion: our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.
Published: 2022

11. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

Author: Joachim Heinrich, Arthur W. Musk, Dan L. Nicolae, Magnus Wickman, Anita L. Kozyrskyj, George T. O'Connor, Sven Michel, John Beilby, Nicole Probst-Hensch, André G. Uitterlinden, Ulrike Gehring, Eugene R. Bleecker, Markku Heliövaara, Christer Janson, Janine Altmüller, Tatsuhiko Tsunoda, Kathleen C. Barnes, Johan G. Eriksson, Alexey Polonikov, Penelope E. Graves, Andrea von Berg, Philip J. Thompson, Sina A. Gharib, Johan C. de Jongste, Miriam F. Moffatt, Adaikalavan Ramasamy, Kristin M. Burkart, Thomas J. Hudson, Marjo-Riitta Järvelin, Rasika A. Mathias, Kathleen M. Donohue, Gonneke Willemsen, Yuliya Fedorova, Michael Kabesch, Jing Hua Zhao, Ashok Kumar, Kenji Matsumoto, Vivi Schlünssen, Dara G. Torgerson, Terri H. Beaty, Florence Demenais, Julie E. Park, Tari Haahtela, Aarno Palotie, Elisabeth Widen, Hamida Mohamdi, Vladimir P. Ivanov, Tarja Laitinen, Emiko Noguchi, Lewis J. Smith, Valérie Siroux, Christopher E. Brightling, P. A. Selivanova, Frank D. Gilliland, Johannes Waage, Deborah A. Meyers, Unnur Thorsteinsdottir, Melanie C. Matheson, Hiroshi Hirose, Sébastien Letort, Andrew Bush, Alan James, Kari Stefansson, Robert A. Scott, Isabelle Romieu, Mads Melbye, Albert M. Levin, Laura R. Loehr, Guo Li, Veikko Salomaa, Celeste Eng, Esteban G. Burchard, Ralf J. P. van der Valk, Bjarke Feenstra, Daan W. Loth, Atsushi Takahashi, Lies Lahousse, Denise Daley, Stephen S. Rich, Carla M. T. Tiesler, Liming Liang, L. Keoki Williams, Susanne Lau, Nicholas J. Wareham, Erik Melén, Cameron D. Palmer, Medea Imboden, Patricia Margaritte-Jeannin, Unnur S. Bjornsdottir, Ludmila M. Ogorodova, Erika von Mutius, Gerard H. Koppelman, Susan R. Heckbert, Rachel A. Myers, Martin Farrall, Moira Chan-Yeung, Jim Gauderman, Frank Geller, Sailaja Vedantam, Rajesh Kumar, Kian Fan Chung, Jon Genuneit, John Henderson, David B. Kantor, Carole Ober, Alexessander Couto Alves, Craig E. Pennell, Inge M. Wouters, Catherine Laprise, Terho Lehtimäki, Colin F. Robertson, Emmanuelle Bouzigon, Maxim B. Freidin, William O.C.M. Cookson, Bruno H. Stricker, John A. Curtin, Albert Hofman, Muhammad T. Salam, Blanca E. Del-Rio-Navarro, Young-Ae Lee, Liesbeth Duijts, Klaus Bønnelykke, Vincent W. V. Jaddoe, Göran Pershagen, Dirkje S. Postma, Pekka Jousilahti, Hans Bisgaard, Dorret I. Boomsma, Amaury Vaysse, Deborah Jarvis, Maria Solodilova, Gudmar Thorleifsson, James J. Yang, V. P. Puzyrev, Manuel A. R. Ferreira, Maartje A.E. Nieuwenhuis, Jouke J. Hottenga, Ingileif Jonsdottir, Graham Jones, Myriam Brossard, Jennie Hui, Judith M. Vonk, Allan B. Becker, Elza Khusnutdinova, Wendy L. McArdle, Benjamin A. Raby, Olli T. Raitakari, Wendy B. White, Mark Lathrop, Adnan Custovic, Ingo Marenholz, Joel N. Hirschhorn, Fernando J. Martinez, Mikko Kuokkanen, Michiaki Kubo, Patrick G. Holt, Torben Sigsgaard, Eskil Kreiner, Stephanie J. London, Daniel F. Gudbjartsson, Mika Kähönen, Guy Brusselle, Blanca E. Himes, R. Graham Barr, Scott T. Weiss, David P. Strachan, Hamdi Mbarek, Wei Ang, A. S. Karunas, Marie Standl, Angela Simpson, Dick Heederik, Zofia K. Z. Gajdos, Raquel Granell, Ani Manichaikul, Fondation Jean-Dausset-CEPH, INSERM U946, Institut National de la Santé et de la Recherche Médicale (INSERM), Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine [Aurora, CO, USA], University of Colorado [Denver], National Heart and Lung Institute (NHLI), Imperial College London, Cologne Center for Genomics (CCG), Cologne Center for Genomics-University of Cologne, Johns Hopkins University (JHU), Pediatrics and Child Health, University of Manitoba [Winnipeg], University of Arizona, King‘s College London, Méthodologie statistique et épidémiologie génétique de maladies multifactorielles, Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Respiratory Medicine and Thoracic Surgery, University of Leicester-Institute for Lung Health, Ghent University Hospital, Department of Paediatric Respiratory Medicine, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], Airway Disease Section, National Heart and Lung Institute, The Generation R Study group, Erasmus University Medical Centre, Medstar Research Institute, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Université Paris-Sorbonne - Paris 4 - École supérieure du professorat et de l'éducation - Académie de Paris (ESPE Paris), Université Paris-Sorbonne (UP4), Population Genetics Laboratory [Tomsk, Russia], Research Institute for Medical Genetics [Tomsk, Russia], University of Southern California (USC), Utrecht University [Utrecht], Institute of Epidemiology, Universität Ulm - Ulm University [Ulm, Allemagne], MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Arizona Respiratory Center, Helsinki University Hospital, Division of Occupational and Environmental Health, Institute for Risk Assessment (IRAS), Ludwig Maximilian University [Munich] (LMU), National Institute of Health and Welfare, MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Mathematics, University of Warwick, Warwick Mathematics Institute (WMI), University of Warwick [Coventry]-University of Warwick [Coventry], Sir Charles Gairdner Hospital, Swiss Tropical and Public Health Institute [Basel], The Generation R Study, Pediatrics, Epidemiology, Uppsala University, Institute of Health Sciences and Biocenter Oulu, University of Oulu, Tampere University Hospital, Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, National Center for Atmospheric Research [Boulder] (NCAR), Epidemiology & Public Health, Swiss Tropical and Public Health Institute [Basel]-Medical School University of Basel, Department of Respiratory Medicine, Departments of Pulmonary Medicine and Medical Genetics, Université du Québec à Chicoutimi (UQAC), McGill University and Genome Quebec Innovation Centre, Department of Pediatric Pneumology and Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Laboratoire des interactions plantes micro-organismes (LIPM), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), China Agricultural University (CAU), Harvard School of Public Health, Department of Epidemiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, National Institute for Environmental Health Sciences Research Triangle Park, National Institute for Materials Science (NIMS), Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], Institute of Environmental Medicine [Stockholm, Sweden], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Center for Human Genomics, Wake Forest University, Université de Tsukuba = University of Tsukuba, Head of Medical Sequencing, Institute of environmental medicine, Karolinska Institute, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centre International de Recherche contre le Cancer (CIRC), Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Aarhus University [Aarhus], Institute of Metabolic Science, MRC, Section of Environment Occupation & Health, University of Manchester [Manchester], Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), deCODE Genetics, deCODE genetics [Reykjavik], Population Health Sciences and Education, St George's University of London, Drug Safety Unit, Inspectorate for Health Care, Tohoku University [Sendai], Department of Oceanography, University of Hawai‘i [Mānoa] (UHM), University of California [San Francisco] (UCSF), University of California, Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, IT University of Copenhagen, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge [UK] (CAM), Sachs’ Children and Youth Hospital [Stockholm, Sweden], Genetic Epidemiology Unit, Addenbrooke's Hospital, University of Illinois [Chicago] (UIC), University of Illinois System, Titu Maiorescu University Bucharest, Titu Maiorescu University = Universitatea Titu Maiorescu [Buchares] (UTM), Pulmonary Medicine, Erasmus MC other, Internal Medicine, Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Vaysse, Amaury, University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), University Children's Hospital-Ludwig-Maximilians University [Munich] (LMU), IT University of Copenhagen (ITU), Groningen Research Institute for Asthma and COPD (GRIAC), Medical Research Council (MRC), National Institute for Health Research, Wellcome Trust, Wareham, Nicholas [0000-0003-1422-2993], Zhao, Jing Hua [0000-0003-4930-3582], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, HAY-FEVER, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, VARIANTS, Australian Asthma Genetics Consortium (AAGC) collaborators, Epigenesis, Genetic, 0302 clinical medicine, Pleiotropy, immune system diseases, Leukocytes, Promoter Regions, Genetic, AUTOIMMUNE-DISEASE, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, Genetics & Heredity, 3. Good health, Histone Code, [SDV] Life Sciences [q-bio], Enhancer Elements, Genetic, Phenotype, TWINS, Hay fever, POPULATIONS, Life Sciences & Biomedicine, Risk, EXPRESSION, Coronacrisis-Taverne, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, Immune system, SDG 3 - Good Health and Well-being, medicine, Genetics, Journal Article, Humans, Genetic Predisposition to Disease, Allele, GENOME-WIDE ASSOCIATION, Alleles, METAANALYSIS, Genetic association, Asthma, Autoimmune disease, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, Rhinitis, Allergic, Seasonal, 06 Biological Sciences, medicine.disease, GENE, respiratory tract diseases, 030104 developmental biology, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, Immunology, Developmental Biology, Genome-Wide Association Study
Abstract: We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
Published: 2018

12. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, Joseph M W, Ittermann, Till, Aulchenko, Yurii S, Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, James, Alan L, Palsson, Stefan Th, Reppe, Sjur, Rotter, Jerome I, Sigurdsson, Gunnar, van Meurs, Joyce B J, Verlaan, Dominique, Williams, Frances M K, Wood, Andrew R, Zhou, Yanhua, Gautvik, Kaare M, Johansson, Ingegerd, Pastinen, Tomi, Raychaudhuri, Soumya, Cauley, Jane A, Chasman, Daniel I, Clark, Graeme R, Cummings, Steven R, Danoy, Patrick, Dennison, Elaine M, Eastell, Richard, Eisman, John A, Juliusdottir, Thorhildur, Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D, Jones, Graeme, Jukema, J Wouter, Khaw, Kay-Tee, Lehtimäki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, Kalafati, Ioanna-Panagiota, Mitchell, Braxton D, Nandakumar, Kannabiran, Nicholson, Geoffrey C, Oostra, Ben A, Peacock, Munro, Pols, Huibert A P, Prince, Richard L, Raitakari, Olli, Reid, Ian R, Robbins, John, Kinnunen, Leena, Sambrook, Philip N, Sham, Pak Chung, Shuldiner, Alan R, Tylavsky, Frances A, van Duijn, Cornelia M, Wareham, Nick J, Cupples, L Adrienne, Econs, Michael J, Evans, David M, Harris, Tamara B, Koenig, Wolfgang, Kung, Annie Wai Chee, Psaty, Bruce M, Reeve, Jonathan, Spector, Timothy D, Streeten, Elizabeth A, Zillikens, M Carola, Thorsteinsdottir, Unnur, Ohlsson, Claes, Karasik, David, Richards, J Brent, Kooner, Ishminder K, Brown, Matthew A, Stefansson, Kari, Uitterlinden, André G, Ralston, Stuart H, Ioannidis, John P A, Kiel, Douglas P, Rivadeneira, Fernando, Sandholm, Niina, Salem, Rany M, McKnight, Amy Jayne, Kratzer, Wolfgang, Brennan, Eoin P, Forsblom, Carol, Isakova, Tamara, McKay, Gareth J, Williams, Winfred W, Sadlier, Denise M, Mäkinen, Ville-Petteri, Swan, Elizabeth J, Palmer, Cameron, Boright, Andrew P, Lamina, Claudia, Ahlqvist, Emma, Deshmukh, Harshal A, Keller, Benjamin J, Huang, Huateng, Ahola, Aila, Fagerholm, Emma, Gordin, Daniel, Harjutsalo, Valma, He, Bing, Heikkilä, Outi, Buchkovich, Martin L, Leander, Karin, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Saraheimo, Markku, Sarti, Cinzia, Lee, Nanette R, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Wadén, Johan, Gill, Geoffrey V, Lichtner, Peter, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Ladenvall, Claes, Alhenc-Gelas, François, Lind, Lars, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Möllsten, Anna, Cimponeriu, Dan, Lindström, Jaana, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Colhoun, Helen M, Panduru, Nicolae Mircea, Lobbens, Stéphane, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Willer, Cristen J, Schmidt, Ellen M, Mach, François, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Mora, Samia, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Magnusson, Patrik Ke, Chang, Hsing-Yi, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Ferreira, Teresa, Fischer, Krista, Mahajan, Anubha, Fontanillas, Pierre, Fraser, Ross M, Freitag, Daniel F, Gurdasani, Deepti, Hyppönen, Elina, Jackson, Anne U, Johansson, Åsa, Johnson, Toby, Heard-Costa, Nancy L, McArdle, Wendy L, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Mihailov, Evelin, Montasser, May E, Menni, Cristina, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K, Shah, Sonia, Merger, Sigrun, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Been, Latonya F, Bolton, Jennifer L, Milani, Lili, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S F, Döring, Angela, Elliott, Paul, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Mills, Rebecca, Gigante, Bruna, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hartikainen, Anna-Liisa, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Monda, Keri L, Kumari, Meena, Langenberg, Claudia, Lin, Shih-Yi, Loos, Ruth J F, Meisinger, Christa, Mooijaart, Simon P, Müller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Mühleisen, Thomas W, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Roman, Tamara S, Mulas, Antonella, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, Tiret, Laurence, Uitterlinden, Andre G, van Pelt, L Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Müller, Gabriele, Wild, Sarah H, Willemsen, Gonneke, Wilsgaard, Tom, Young, Elizabeth H, Zhao, Jing Hua, Adair, Linda S, Arveiler, Dominique, Assimes, Themistocles L, Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O, Boomsma, Dorret I, Borecki, Ingrid B, Bornstein, Stefan R, Bovet, Pascal, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chen, Yii-Der Ida, Collins, Francis S, Cooper, Richard S, Danesh, John, de Faire, Ulf, Feranil, Alan B, Ferrières, Jean, Ferrucci, Luigi, Nalls, Michael A, Freimer, Nelson B, Gieger, Christian, Groop, Leif C, Gyllensten, Ulf, Hamsten, Anders, Hingorani, Aroon, Hovingh, G Kees, Hsiung, Chao Agnes, Humphries, Steve E, Hveem, Kristian, Iribarren, Carlos, Järvelin, Marjo-Riitta, Jula, Antti, Kaprio, Jaakko, Glorioso, Nicola, Kesäniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S, Koudstaal, Peter J, Krauss, Ronald M, Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O, Laakso, Markku, Lakka, Timo A, Lindgren, Cecilia M, Martin, Nicholas G, März, Winfried, McCarthy, Mark I, McKenzie, Colin A, Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D, Olden, Matthias, Munroe, Patricia B, Njølstad, Inger, Pedersen, Nancy L, Power, Chris, Pramstaller, Peter P, Price, Jackie F, Quertermous, Thomas, Rauramaa, Rainer, Saleheen, Danish, Rayner, Nigel W, Salomaa, Veikko, Sanghera, Dharambir K, Saramies, Jouko, Schwarz, Peter E H, Sheu, Wayne H-H, Siegbahn, Agneta, Spector, Tim D, Strachan, David P, Drong, Alexander W, Renstrom, Frida, Tayo, Bamidele O, Tremoli, Elena, Uusitupa, Matti, Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J, Whitfield, John B, Wolffenbuttel, Bruce H R, Ried, Janina S, Ordovas, Jose M, Boerwinkle, Eric, Palmer, Colin N A, Franks, Paul W, Ripatti, Samuli, Sandhu, Manjinder S, Robertson, Neil R, Rich, Stephen S, Boehnke, Michael, Deloukas, Panos, Kathiresan, Sekar, Mohlke, Karen L, Ingelsson, Erik, Abecasis, Gonçalo R, Abecasis, Gonçalo, Caulfield, Mark, Chasman, Dan, Ehret, Georg, Johnson, Andrew, Johnson, Louise, Larson, Martin, Levy, Daniel, Munroe, Patricia, Newton-Cheh, Christopher, O'Reilly, Paul, Palmas, Walter, Psaty, Bruce, Rice, Kenneth, Smith, Albert, Snider, Harold, Tobin, Martin, Van Duijn, Cornelia, Verwoert, Germaine, Rice, Kenneth M, Johnson, Andrew D, Tobin, Martin D, Verwoert, Germaine C, Hwang, Shih-Jen, Pihur, Vasyl, Scholtens, Salome, O'Reilly, Paul F, Teumer, Alexander, Glazer, Nicole L, Launer, Lenore, Aulchenko, Yurii, Heath, Simon, Sennblad, Bengt, Sõber, Siim, Parsa, Afshin, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Peden, John F, Seufferlein, Thomas, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N, Fava, Cristiano, Fox, Ervin R, Sitlani, Colleen M, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H, Smith, Albert Vernon, Shi, Gang, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Nguyen, Khanh-Dung Hoang, Matullo, Giuseppe, Gaunt, Tom R, Onland-Moret, N Charlotte, Cooper, Matthew N, Platou, Carl G P, Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S, Kuznetsova, Tatiana, Stringham, Heather M, Uiterwaal, Cuno S P M, Adeyemo, Adebowale, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D, Sundström, Johan, Chang, Yen-Pei C, Steinle, Nanette I, Grobbee, Diederick E, Arking, Dan E, Kardia, Sharon L, Morrison, Alanna C, Najjar, Samer, Swertz, Morris A, Hadley, David, Brown, Morris J, Connell, John M, Hingorani, Aroon D, Day, Ian N M, Lawlor, Debbie A, Beilby, John P, Lawrence, Robert W, Clarke, Robert, Collins, Rory, Hopewell, Jemma C, Ongen, Halit, Dreisbach, Albert W, Li, Yali, Young, J. H., Bis, Joshua C, Syvänen, Ann-Christine, Chen, Ming-Huei, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M, Islam, Muhammad, Jafar, Tazeen H, Erdmann, Jeanette, Kulkarni, Smita R, Grässler, Jürgen, Howard, Philip, Thorand, Barbara, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Weder, Alan B, Sun, Yan V, Bergman, Richard N, Scott, Laura J, Peltonen, Leena, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A, Wang, Thomas J, Tomaschitz, Andreas, Burton, Paul R, Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K, Rudock, Megan E, Heckbert, Susan R, Smith, Nicholas L, Troffa, Chiara, Wiggins, Kerri L, Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairajan, Tripathy, Vikal, Langefeld, Carl D, Rosengren, Annika, van Oort, Floor Va, Thelle, Dag S, Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Verweij, Niek, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H-Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Vonk, Judith M, Scott, James, Sehmi, Joban S, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Stanèáková, Alena, Raffel, Leslie J, Yao, Jie, O'Donnell, Chris, Schwartz, Stephen M, Ikram, M Arfan, Longstreth, W. T., Mosley, Thomas H, Seshadri, Sudha, Shrine, Nick R G, Wain, Louise V, Wennauer, Roman, Morken, Mario A, Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A, Rasheed, Asif, Goel, Anuj, Watkins, Hugh, Bakker, Stephan J L, van Gilst, Wiek H, Janipalli, Charles S, Mani, K Radha, Yajnik, Chittaranjan S, Mattace-Raso, Francesco U S, Wojczynski, Mary K, Demirkan, Ayse, Lakatta, Edward G, Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Ong, Rick Twee-Hee, Dörr, Marcus, Kroemer, Heyo K, Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Day, Felix R, Zhang, Qunyuan, Zelenika, Diana, Zhai, Guangju, Meschia, James F, Sharma, Pankaj, Terzic, Janos, Kumar, M J Kranthi, Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E, Fowkes, F Gerald R, Charchar, Fadi J, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L, Brand, Eva, Samani, Nilesh J, Polasek, Ozren, Talmud, Philippa J, Nyberg, Fredrik, Laan, Maris, Palmer, Lyle J, van der Schouw, Yvonne T, Choi, Murim, Casas, Juan P, Vineis, Paolo, Ganesh, Santhi K, Wong, Tien Y, Tai, E Shyong, Rao, Dabeeru C, Eriksson, Per, Morris, Richard W, Dominiczak, Anna F, Marmot, Michael G, Miki, Tetsuro, Chandak, Giriraj R, Coresh, Josef, Navis, Gerjan, Folkersen, Lasse, Han, Bok-Ghee, Zhu, Xiaofeng, Melander, Olle, Gyllensten, Ulf B, Wright, Alan F, Franco-Cereceda, Anders, Farrall, Martin, Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J G, Altshuler, David, Gharavi, Ali G, Rettig, Rainer, Uda, Manuela, Witteman, Jacqueline C M, Hedman, Åsa K, Vasan, Ramachandran S, Larson, Martin G, Hivert, Marie-France, Caulfield, Mark J, Anderson, Carl A, Gordon, Scott D, Guo, Qun, Henders, Anjali K, Esko, Tonu, Huang, Jinyan, Lambert, Ann, Lee, Sang Hong, Kraft, Peter, Kennedy, Stephen H, Macgregor, Stuart, Missmer, Stacey A, Montgomery, Grant W, Morris, Andrew P, Nyholt, Dale R, Painter, Jodie N, Roseman, Fenella, Treloar, Susan A, Visscher, Peter M, Wallace, Leanne, Zondervan, Krina T, Alizadeh, Behrooz Z, de Boer, Rudolf A, Boezen, H Marike, Bruinenberg, Marcel, Karpe, Fredrik, Franke, Lude, van der Klauw, Melanie M, Ormel, Johan, Postma, Dirkje S, Rosmalen, Judith G M, Slaets, Joris P, Keildson, Sarah, Stolk, Ronald P, Scott, Robert A, Lagou, Vasiliki, Welch, Ryan P, Wheeler, Eleanor, Mägi, Reedik, Kiryluk, Krzysztof, Rehnberg, Emil, Rasmussen-Torvik, Laura J, Yengo, Loïc, Lecoeur, Cecile, Liang, Liming, Johnson, Paul C D, Hottenga, Jouke-Jan, Lifton, Richard P, Salo, Perttu, Timpson, Nicholas J, St Pourcain, Beate, Andrews, Jeanette S, Hui, Jennie, Bielak, Lawrence F, Ma, Baoshan, Zhao, Wei, Horikoshi, Momoko, Navarro, Pau, Esko, Tönu, McKnight, Amy J, Fall, Tove, Chen, Han, Robertson, Neil, Rybin, Denis, McPherson, Ruth, Willems, Sara M, Chines, Peter S, Kang, Hyun Min, Song, Kijoung, Croteau-Chonka, Damien C, An, Ping, Marullo, Letizia, Jansen, Hanneke, Oldehinkel, Albertine J, Min, Josine L, Pankow, James S, North, Kari E, Forouhi, Nita G, Edkins, Sarah, Varga, Tibor V, Oksa, Heikki, Antonella, Mulas, Moffatt, Miriam F, Kong, Augustine, Herder, Christian, Antti, Jula, Small, Kerrin, Miljkovic, Iva, Atalay, Mustafa, Kiess, Wieland, Murabito, Joanne M, Smit, Johannes H, Campbell, Susan, Fowkes, Gerard R, Nicholson, George, Kovacs, Peter, Zemunik, Tatijana, Basart, Hanneke V, Rathmann, Wolfgang, Maerz, Winfried, Peters, Annette, Province, Michael A, Hastie, Nicholas D, Olsson, Christian, Stumvoll, Michael, Waterworth, Dawn M, Watanabe, Richard M, de Geus, Eco J C, Penninx, Brenda W, Perry, John Rb, Reinmaa, Eva, Dedoussis, George V, Kutalik, Zoltán, Toenjes, Anke, Peyser, Patricia A, Körner, Antje, Keinanen-Kiukaanniemi, Sirkka M, Schadt, Eric E, Saaristo, Timo E, Dupuis, Josée, Sattar, Naveed, Cucca, Francesco, Balkau, Beverley, Froguel, Philippe, Jarvelin, Marjo-Riitta, Bouatia-Naji, Nabila, Stolk, Lisette, Meigs, James B, Ahmadi, Kourosh R, Ainali, Chrysanthi, Barrett, Amy, Vallejo, Edgar E, Bataille, Veronique, Bell, Jordana T, Buil, Alfonso, Dermitzakis, Emmanouil T, Dimas, Antigone S, Durbin, Richard, Glass, Daniel, Hassanali, Neelam, Westra, Harm-Jan, Ingle, Catherine, Knowles, David, Krestyaninova, Maria, Lowe, Christopher E, Meduri, Eshwar, di Meglio, Paola, Montgomery, Stephen B, Nestle, Frank O, Nica, Alexandra C, Nisbet, James, O'Rahilly, Stephen, Parts, Leopold, Potter, Simon, Sekowska, Magdalena, Shin, So-Youn, Consortium, ADIPOGen, Small, Kerrin S, Surdulescu, Gabriela, Travers, Mary E, Tsaprouni, Loukia, Tsoka, Sophia, Wilk, Alicja, Yang, Tsun-Po, Consortium, CARDIOGRAMplusC4D, Matise, Tara, Buyske, Steve, Higashio, Julia, Williams, Rasheeda, Nato, Andrew, Ambite, Jose Luis, Deelman, Ewa, Manolio, Teri, Hindorff, Lucia, Consortium, CKDGen, Heiss, Gerardo, Taylor, Kira, Franceschini, Nora, Avery, Christy, Graff, Misa, Lin, Danyu, Quibrera, Miguel, Cochran, Barbara, Kao, Linda, Umans, Jason, Consortium, GEFOS, Cole, Shelley, MacCluer, Jean, Person, Sharina, Pankow, James, Gross, Myron, Fornage, Myriam, Durda, Peter, Jenny, Nancy, Patsy, Bruce, Consortium, GENIE, Arnold, Alice, Buzkova, Petra, Crawford, Dana, Haines, Jonathan, Murdock, Deborah, Glenn, Kim, Brown-Gentry, Kristin, Thornton-Wells, Tricia, Dumitrescu, Logan, Jeff, Janina, GLGC, Bush, William S, Mitchell, Sabrina L, Goodloe, Robert, Wilson, Sarah, Boston, Jonathan, Malinowski, Jennifer, Restrepo, Nicole, Oetjens, Matthew, Fowke, Jay, Zheng, Wei, ICBP, Spencer, Kylee, Ritchie, Marylyn, Pendergrass, Sarah, Le Marchand, Loïc, Wilkens, Lynne, Park, Lani, Tiirikainen, Maarit, Kolonel, Laurence, Lim, Unhee, Cheng, Iona, Consortium, International Endogene, Wang, Hansong, Shohet, Ralph, Haiman, Christopher, Stram, Daniel, Henderson, Brian, Monroe, Kristine, Schumacher, Fredrick, Peters, Ulrike, Anderson, Garnet, Study, LifeLines Cohort, Carlson, Chris, Prentice, Ross, LaCroix, Andrea, Wu, Chunyuan, Carty, Cara, Gong, Jian, Rosse, Stephanie, Young, Alicia, Haessler, Jeff, Kocarnik, Jonathan, Investigators, MAGIC, Lin, Yi, Jackson, Rebecca, Duggan, David, Kuller, Lew, Perry, John R B, He, Chunyan, Sulem, Patrick, Consortium, MuTHER, Barbalic, Maja, Broer, Linda, Byrne, Enda M, Ernst, Florian, Gudbjartsson, Daniel F, McArdle, Patick F, Consortium, PAGE, Porcu, Eleonora, van Wingerden, Sophie, Zhuang, Wei V, Albrecht, Eva, Randall, Joshua C, Consortium, ReproGen, Lauc, Lovorka Barac, Boban, Mladen, Broekmans, Frank J, Burri, Andrea, Chanock, Stephen J, Chen, Constance, Cornelis, Marilyn C, Amouyel, Philippe, Corre, Tanguy, Coviello, Andrea D, d'Adamo, Pio, Davies, Gail, Deary, Ian J, Dedoussis, George V Z, Deloukas, Panagiotis, Ebrahim, Shah, Eiriksdottir, Gudny, Eriksson, Johan G, Fauser, Bart C J M, Ferreli, Liana, Folsom, Aaron R, Garcia, Melissa E, Gasparini, Paolo, Bakker, Stephan Jl, Glazer, Nicole, Hall, Per, Haller, Toomas, Hankinson, Susan E, Hass, Merli, Heath, Andrew C, Beilby, John, Janssens, A Cecile J W, Kardia, Sharon L R, Keyzer, Jules, Kolcic, Ivana, Lahti, Jari, Lai, Sandra, Laisk, Triin, Laven, Joop S E, Liu, Jianjun, Lopez, Lorna M, Louwers, Yvonne V, Marongiu, Mara, Blangero, John, Klaric, Irena Martinovic, Masciullo, Corrado, McKnight, Barbara, Medland, Sarah E, Melzer, David, Newman, Anne B, Paré, Guillaume, Peeters, Petra H M, Pistis, Giorgio, Plump, Andrew S, Pop, Victor J M, Räikkönen, Katri, Sala, Cinzia, Salumets, Andres, Smith, Jennifer A, Stacey, Simon N, Starr, John M, Stathopoulou, Maria G, Styrkarsdottir, Unnur, Tenesa, Albert, Scherag, André, Toniolo, Daniela, Tryggvadottir, Laufey, Tsui, Kim, Ulivi, Sheila, van Dam, Rob M, van Gils, Carla H, van Nierop, Peter, Vink, Jacqueline M, Voorhuis, Marlies, Waeber, Gérard, Wallaschofski, Henri, Wichmann, H Erich, Widen, Elisabeth, Wijnands-van Gent, Colette J M, Claudi-Boehm, Simone, Zgaga, Lina, Zygmunt, Marek, Arnold, Alice M, Buring, Julie E, Crisponi, Laura, Demerath, Ellen W, Hu, Frank B, Hunter, David J, Launer, Lenore J, Crawford, Dana C, Schlessinger, David, Murray, Anna, Visser, Jenny A, Lunetta, Kathryn L, Elks, Cathy E, Cousminer, Diana L, Feenstra, Bjarke, Lin, Peng, de Geus, Eco Jc, McArdle, Patrick F, van Wingerden, Sophie W, Smith, Erin N, Ulivi, Shelia, Warrington, Nicole M, Alavere, Helen, Erbel, Raimund, Barroso, Ines, Berenson, Gerald S, Blackburn, Hannah, Busonero, Fabio, Chen, Wei, Couper, David, Easton, Douglas F, Eriksson, Johan, Foroud, Tatiana, Geller, Frank, Ferrannini, Ele, Hernandez, Dena G, Kilpeläinen, Tuomas O, Li, Shengxu, Melbye, Mads, Murray, Jeffrey C, Murray, Sarah S, Nelis, Mari, Ness, Andrew R, Northstone, Kate, Franco, Oscar H, Pennell, Craig E, Pharoah, Paul, Rafnar, Thorunn, Rice, John P, Ring, Susan M, Gansevoort, Ron T, Schork, Nicholas J, Segrè, Ayellet V, Sovio, Ulla, Srinivasan, Sathanur R, Tammesoo, Mar-Liis, Tikkanen, Emmi, Tyrer, Jonathon, van Meurs, Joyve B J, Waeber, Gerard, Weedon, Michael N, Haiman, Christopher A, Young, Lauren, Zhuang, Wei Vivian, Bierut, Laura J, Boyd, Heather A, Hattersley, Andrew T, Schreiber, Stefan, Heliövaara, Markku, Hoffmann, Wolfgang, Homuth, Georg, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M, Kee, Frank, Fehrmann, Rudolf, Kraja, Aldi T, Kuulasmaa, Kari, Le Marchand, Loic, Karjalainen, Juha, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C, Musk, Arthur W, Möhlenkamp, Stefan, Kahali, Bratati, Raitakari, Olli T, Rankinen, Tuomo, Rao, D. C., Rice, Treva K, Ritchie, Marylyn D, Sarzynski, Mark A, Schwarz, Peter Eh, Steinthorsdottir, Valgerdur, Strauch, Konstantin, Tönjes, Anke, Tremblay, Angelo, Vohl, Marie-Claude, Witteman, Jacqueline C, Bouchard, Claude, Cauchi, Stéphane, Grabe, Hans-Jörgen, Jöckel, Karl-Heinz, Anderson, Denise, Palmer, Colin Na, Beekman, Marian, Pérusse, Louis, Sinisalo, Juha, Veronesi, Giovanni, Buyske, Steven, Walker, Mark, Abecasis, Goncalo R, Berndt, Sonja I, Kaplan, Robert C, Qi, Lu, Locke, Adam E, Yang, Jian, Speliotes, Elizabeth K, Fox, Caroline S, Heid, Iris M, Loos, Ruth Jf, Dastani, Zari, Timpson, Nicholas, Yuan, Xin, Henneman, Peter, Kizer, Jorge R, Lyytikainen, Leo-Pekka, Fuchsberger, Christian, Coassin, Stefan, Lohman, Kurt, Uh, Hae-Won, Bidulescu, Aurelian, Greenwood, Celia M T, Ladouceur, Martin, Grimsby, Jonna, Manning, Alisa K, Kooner, Jaspal, Mooser, Vincent E, Kapur, Karen A, Chambers, John, Frants, Rune, Willemsvan-vanDijk, Ko, Kristiansson, Kati, Winkler, Thomas, Tracy, Russell P, Brody, Jennifer, Chen, Ida, Wood, Andy, Carlson, Olga D, Egan, Josephine M, Böhringer, Stefan, van Heemst, Diana, Kedenko, Lyudmyla, Leach, Irene Mateo, Nuotio, Marja-Liisa, Loo, Britt-Marie, Harris, Tamara, Kanaya, Alka, Haun, Margot, Katsareli, Efi, Medina-Gomez, Carolina, Couper, David J, Duncan, Bruce B, Kloppenburg, Margreet, Borja, Judith B, Wilson, James G, Musani, Solomon, Semple, Robert, Allison, Matthew A, Redline, Susan, Buxbaum, Sarah G, Meulenbelt, Ingrid, Ballantyne, Christie M, Pasko, Dorota, Paulweber, Bernhard, Pechlivanis, Sonali, Siscovick, David S, Kronenberg, Florian, van Duijn, Cornelia, Peters, Marjolein J, Dupuis, Josee, Richards, John Brent, Willenborg, Christina, Thompson, John R, Goldstein, Benjamin A, König, Inke R, Cazier, Jean-Baptiste, Hall, Alistair S, Havulinna, Aki S, Ho, Weang K, Eriksson, Niclas, Sung, Yun Ju, Lundmark, Per, Rafelt, Suzanne, Van Zuydam, Natalie, Ziegler, Andreas, Balmforth, Anthony J, Burgdorf, Christof, Cox, David, El Mokhtari, NourEddine, Van Vliet-Ostaptchouk, Jana V, Hager, Jörg, Hunt, Sarah E, Kang, Hyun M, Kessler, Thorsten, Knowles, Joshua W, Kolovou, Genovefa, Langford, Cordelia, Lokki, Marja-Liisa, Lundmark, Anders, Maouche, Seraya, Nikus, Kjell, Rayner, N William, Rosinger, Silke, Rubin, Diana, Rumpf, Moritz P, Schäfer, Arne, Sivananthan, Mohan, Stewart, Alexandre F R, Tan, Sian-Tsung, Thorgeirsson, Gudmundur, van der Schoot, C Ellen, Wagner, Peter J, Wells, George A, Wild, Philipp S, Ärnlöv, Johan, Basart, Hanneke, Cambien, Francois, Cupples, Adrienne L, Arscott, Gillian M, Diemert, Patrick, Evans, Alun, Ferrario, Marco M, Gauguier, Dominique, Go, Alan S, Goodall, Alison H, Gudnason, Villi, Hazen, Stanley L, Jang, Yangsoo, Kim, Hyo-Soo, Laaksonen, Reijo, Lee, Ji-Young, Ouwehand, Willem H, Parish, Sarah, Park, Jeong E, Bellis, Claire, Schadt, Eric, Shah, Svati H, Stark, Klaus, Trégouët, David-Alexandre, Virtamo, Jarmo, Bennett, Amanda J, Wareham, Nicholas, Zimmermann, Martina E, Nieminen, Markku S, Hengstenberg, Christian, Berne, Christian, Zalloua, Pierre A, Blankenberg, Stefan S, Pers, Tune H, Blüher, Matthias, O'Donnell, Christopher, Roberts, Robert, Schunkert, Heribert, Garnaas, Maija, Böger, Carsten A, Bonnet, Fabrice, Tin, Adrienne, Taliun, Daniel, Li, Man, Gao, Xiaoyi, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Böttcher, Yvonne, Foster, Meredith C, O'Seaghdha, Conall M, Struchalin, Maksim, Gierman, Hinco J, Feitosa, Mary, Atkinson, Elizabeth J, Carba, Delia B, Chouraki, Vincent, Holliday, Elizabeth G, Sorice, Rossella, Kutalik, Zoltan, Deshmukh, Harshal, Chu, Audrey Y, Murgia, Federico, Caspersen, Ida H, Imboden, Medea, Kollerits, Barbara, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, de Andrade, Mariza, Turner, Stephen T, Ding, Jingzhong, Daw, E Warwick, Freedman, Barry I, Wichmann, H -Erich, Minelli, Cosetta, Wheeler, Heather E, Deelen, Joris, Zaboli, Ghazal, Ellinghaus, David, Nöthlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Endlich, Karlhans, Nauck, 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Surdulescu, G., Travers, ME., Tsaprouni, L., Tsoka, S., Wilk, A., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., Heiss, G., Taylor, K., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Crawford, D., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Ritchie, M., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Peters, U., Anderson, G., Carlson, C., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, 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(INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Department of Pharmacy Sciences, Creighton University Medical Center, Medical Department III, Universität Leipzig, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Public Health and Clinical Medicine, Medstar Research Institute, Genetics and Pathology, Finnish Institute of Occupational Health, Epidemiology, University Medical Centre Groningen, Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California [Irvine] (UC Irvine), Department of Odontology, Cariology, Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Division of Cardiology, Geneva University Hospital (HUG), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Anaesthesia and Intensive care, Royal Aberdeen Childrens Hospital, UCL Institute of neurology, UCL Institute of Neurology, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], 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= University of Helsinki, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, MRC epidemiology Unit, Institute of Epidemiology, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Oncology, Queensland Brain Institute, University of Queensland [Brisbane], Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, 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(BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Landsteiner Laboratory, Clinical Haematology, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Lund University Diabetes Centre-Lund University [Lund], Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Technical University of Denmark [Lyngby] (DTU), Université de Lausanne (UNIL), Universität Duisburg-Essen [Essen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [Berkeley], University of California-University of California, Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche 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Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej Bedrac, S, Nguyen, T, Nogues, X, Patel, M, Prezelj, J, Scollen, S, Siggeirsdottir, K, Svensson, O, Trummer, O, van Schoor, N, Woo, J, Zhu, K, Balcells, S, Brandi, M, Cheng, S, Christiansen, C, Cooper, C, Frost, M, Goltzman, D, González Macías, J, Karlsson, M, Khusnutdinova, E, Koh, J, Kollia, P, Langdahl, B, Leslie, W, Lips, P, Ljunggren, Ö, Lorenc, R, Marc, J, Mellström, D, Obermayer Pietsch, B, Olmos, J, Pettersson Kymmer, U, Reid, D, Riancho, J, Rousseau, F, Tang, N, Urreizti, R, Van Hul, W, Zarrabeitia, M, Castano Betancourt, M, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina Gómez, C, Palsson, S, Reppe, S, Sigurdsson, G, van Meurs, J, Verlaan, D, Williams, F, Zhou, Y, Gautvik, K, Raychaudhuri, S, Cauley, J, Clark, G, Cummings, S, Danoy, P, Dennison, E, Eastell, R, Eisman, J, Jackson, R, Jones, G, Khaw, K, Mccloskey, E, Nandakumar, K, Peacock, M, Pols, H, Prince, R, Reid, I, Robbins, J, Sambrook, P, Sham, P, Tylavsky, F, Econs, M, Kung, A, Reeve, J, Streeten, E, Karasik, D, Ralston, S, Ioannidis, J, Kiel, D, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Mäkinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkilä, O, Hietala, K, Kytö, J, Lahermo, P, Lehto, M, Österholm, A, Parkkonen, M, Pitkäniemi, J, Rosengård Bärlund, M, Saraheimo, M, Sarti, C, Söderlund, J, Soro Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Wadén, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Tregouet, D, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Möllsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Fraser, R, Freitag, D, Gurdasani, D, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Van den Herik, E, Volcik, K, Asiki, G, Been, L, Bolton, J, Bonnycastle, L, Burnett, M, Cesana, G, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Kastelein, J, Kim, E, Komulainen, P, Lin, S, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Stančáková, A, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Willemsen, G, Young, E, Bennett, F, Boomsma, D, Bovet, P, Chen, Y, Feranil, A, Freimer, N, Hsiung, C, Järvelin, M, Kesäniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Martin, N, Meneton, P, Moilanen, L, Njølstad, I, Price, J, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sõber, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjögren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Grässler, J, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Stanèáková, A, Raffel, L, Yao, J, Schwartz, S, Ikram, M, Longstreth W., J, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Morken, M, Laitinen, J, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Würtz, P, Ong, R, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Dominiczak, A, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Anderson, C, Gordon, S, Guo, Q, Henders, A, Lambert, A, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Alizadeh, B, de Boer, R, Boezen, H, van der Klauw, M, Ormel, J, Postma, D, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Lecoeur, C, Johnson, P, Hottenga, J, Salo, P, Bielak, L, Zhao, W, Horikoshi, M, Navarro, P, Chen, H, Rybin, D, Song, K, An, P, Marullo, L, Jansen, H, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Toenjes, A, Peyser, P, Körner, A, Cucca, F, Balkau, B, Bouatia Naji, N, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Hedman, Å, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Higashio, J, Williams, R, Nato, A, Ambite, J, Manolio, T, Hindorff, L, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown Gentry, K, Thornton Wells, T, Dumitrescu, L, Jeff, J, Bush, W, Mitchell, S, Goodloe, R, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Zheng, W, Spencer, K, Pendergrass, S, Wilkens, L, Park, L, Tiirikainen, M, Kolonel, L, Lim, U, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Schumacher, F, Anderson, G, Carlson, C, Prentice, R, Wu, C, Carty, C, Gong, J, Rosse, S, Young, A, Haessler, J, Kocarnik, J, Lin, Y, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chanock, S, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hall, P, Hankinson, S, Hass, M, Heath, A, Janssens, A, Keyzer, J, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Medland, S, Melzer, D, Newman, A, Paré, G, Peeters, P, Pop, V, Räikkönen, K, Salumets, A, Smith, J, Stacey, S, Starr, J, Stathopoulou, M, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Wallaschofski, H, Widen, E, Wijnands van Gent, C, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Feenstra, B, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Easton, D, Foroud, T, Geller, F, Kilpeläinen, T, Li, S, Melbye, M, Murray, J, Murray, S, Ness, A, Northstone, K, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segrè, A, Sovio, U, Srinivasan, S, Tammesoo, M, Tyrer, J, Weedon, M, Young, L, Bierut, L, Boyd, H, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Adipose Tissue/metabolism, Male, genetic association, subcutaneous fat, Transcription, Genetic, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Humans, Insulin, Insulin Resistance, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Waist-Hip Ratio, Body Fat Distribution, Genome-Wide Association Study, Multidisciplinary, Insulin Resistance/genetics, Genome-wide association study, Continental Population Groups/genetics, genetic analysis, heritability, gene cluster, Science::Biological sciences::Human anatomy and physiology [DRNTU], 0302 clinical medicine, high density lipoprotein cholesterol, Models, genetics [Insulin Resistance], histone modification, Age Factor, insulin receptor, 0303 health sciences, Adipocyte, Human/genetics, CARDIOGRAMplusC4D Consortium, ADIPOGENIC DIFFERENTIATION, genetic correlation, body fat, Continental Population Group, priority journal, 5 trisphosphate 3 phosphatase, GEFOS Consortium, meta analysis (topic), Science & Technology - Other Topics, ddc:500, transcription regulation, Adipogenesis/genetics, Single Nucleotide/genetics, Human, medicine.medical_specialty, Waist, phosphatidylinositol 3, European, ta3111, genetic regulation, Article, developmental biology, 03 medical and health sciences, MAGIC Investigators, transcription initiation site, SDG 3 - Good Health and Well-being, Genetic, genomics, GLYCEMIC TRAITS, genetics [Continental Population Groups], Polymorphism, GENOME-WIDE ASSOCIATION, Physiologic, genetics [Adipogenesis], Adipocytes/metabolism, Europe/ethnology, Genome, Human/genetics, Insulin/metabolism, Neovascularization, Physiologic/genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Transcription, Genetic/genetics, Genetic/genetics, Adipogenesi, Science & Technology, adiponectin, [ SDV ] Life Sciences [q-bio], vasculotropin, genetics [Quantitative Trait Loci], ta1184, Racial Groups, ta1182, gene mapping, ta3121, triacylglycerol blood level, medicine.disease, Biological, major clinical study, amino acid sequence, metabolism [Insulin], Endocrinology, metabolism [Adipocytes], genetic loci, insulin, body fat, GLGC, International Endogene Consortium, metabolism [Adipose Tissue], Body mass index, HUMAN HEIGHT, Epigenesis, LifeLines Cohort Study, ReproGen Consortium, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, tissue level, Physiologic/genetics, [SDV]Life Sciences [q-bio], Medizin, Adipose tissue, low density lipoprotein cholesterol, PAGE Consortium, COMMON SNPS, angiogenesis, Waist–hip ratio, genetics [Obesity], MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, single nucleotide polymorphism, fat, genetic variability, molecular biology, body mass index (BMI), ethnology [Europe], peroxisome proliferator activated receptor, 2. Zero hunger, Genetics, Genome, Single Nucleotide, waist circumference, insulin, phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, triacylglycerol, vasculotropin, developmental biology, gene expression, genome, numerical model, adipocyte, adipose tissue, body fat distribution, body mass, female, gene locus, gene structure, hip circumference, human, insulin resistance, lipoprotein blood level, male, obesity, protein protein interaction, sex difference, waist hip ratio, Multidisciplinary Sciences, genetics [Transcription, Genetic], genetics [Polymorphism, Single Nucleotide], ADIPOGen Consortium, genetics [Neovascularization, Physiologic], Transcription, SUSCEPTIBILITY LOCI, General Science & Technology, ICBP, 030209 endocrinology & metabolism, Biology, adipocyte, MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, MESENCHYMAL STEM-CELLS, GENIE Consortium, SEXUAL-DIMORPHISM, Insulin resistance, Internal medicine, medicine, genetics [Genome, Human], ABDOMINAL ADIPOSITY, Neovascularization, 030304 developmental biology, FALSE DISCOVERY, CKDGen Consortium, Sex Characteristic, MuTHER Consortium, numerical model
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P
Published: 2015

13. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, Thomas W, Justice, Anne E, Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F, Chu, Su, Czajkowski, Jacek, Esko, Tõnu, Fall, Tove, Kilpeläinen, Tuomas O, Lu, Yingchang, Mägi, Reedik, Mihailov, Evelin, Pers, Tune H, Rüeger, Sina, Teumer, Alexander, Ehret, Georg B, Ferreira, Teresa, Heard-Costa, Nancy L, Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D, Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M, Jansen, Rick, Westra, Harm-Jan, White, Charles C, Absher, Devin, Ahluwalia, Tarunveer S, Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L, de Craen, Anton JM, Bis, Joshua C, Bonnefond, Amélie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston WK, Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E, Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B, Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E, Jackson, Anne U, Jacobs, Kevin B, Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E, Lahti, Jari, Mateo Leach, Irene, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela AF, Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L, Montasser, May E, Müller, Gabriele, Müller-Nurasyid, Martina, Nolte, Ilja M, Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W, Renström, Frida, Rizzi, Federica, Rose, Lynda M, Ryan, Kathy A, Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stančáková, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P, Vandenput, Liesbeth, van der Laan, Sander W, van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L, Wang, Sophie R, Wang, Zhaoming, Wild, Sarah H, Willenborg, Christina, Wilson, James F, Wong, Andrew, Yang, Jian, Yengo, Loïc, Yerges-Armstrong, Laura M, Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A, Bakker, Stephan JL, Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blüher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L, Boyd, Heather A, Bruinenberg, Marcel, Buchman, Aron S, Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S, Claudi-Boehm, Simone, Cole, John, Collins, Francis S, de Geus, Eco JC, de Groot, Lisette CPGM, Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G, Friedrich, Nele, Gejman, Pablo V, Gigante, Bruna, Glorioso, Nicola, Go, Alan S, Gottesman, Omri, Gräßler, Jürgen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T, Heath, Andrew C, Henders, Anjali K, Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G, Hui, Jennie, Husemoen, Lise L, Hutri-Kähönen, Nina, Hysi, Pirro G, Illig, Thomas, De Jager, Philip L, Jalilzadeh, Shapour, Jørgensen, Torben, Jukema, J Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J, Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T, Kratzer, Wolfgang, Krüger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J, Leander, Karin, Lindström, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stéphane, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Magnusson, Patrik K, McArdle, Wendy L, Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W, Morris, Andrew P, Narisu, Narisu, Nelis, Mari, Ong, Ken K, Palotie, Aarno, Pérusse, Louis, Pichler, Irene, Pilia, Maria G, Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M, Rice, Treva K, Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R, Sarzynski, Mark A, Scholtens, Salome, Scott, Robert A, Scott, William R, Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P Eline, Smit, Jan H, Sparsø, Thomas H, Stirrups, Kathleen, Stolk, Ronald P, Stringham, Heather M, Swertz, Morris A, Swift, Amy J, Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J, Völker, Uwe, Vohl, Marie-Claude, Vonk, Judith M, Waldenberger, Melanie, Walker, Ryan W, Wennauer, Roman, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F, Zillikens, M Carola, van Dijk, Suzanne C, van Schoor, Natasja M, Asselbergs, Folkert W, de Bakker, Paul IW, Beckmann, Jacques S, Beilby, John, Bennett, David A, Bergman, Richard N, Bergmann, Sven, Böger, Carsten A, Boehm, Bernhard O, Boerwinkle, Eric, Boomsma, Dorret I, Bornstein, Stefan R, Bottinger, Erwin P, Bouchard, Claude, Chambers, John C, Chanock, Stephen J, Chasman, Daniel I, Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G, Evans, Denis A, de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W, Froguel, Philippe, Gansevoort, Ron T, Gieger, Christian, Grönberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliövaara, Markku, Hengstenberg, Christian, Hicks, Andrew A, Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V, Hveem, Kristian, James, Alan L, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus ALM, Kivimaki, Mika, Knekt, Paul B, Koistinen, Heikki A, Kooner, Jaspal S, Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G, Laakso, Markku, Lakka, Timo A, Lehtimäki, Terho, Lettre, Guillaume, Levinson, Douglas F, Lind, Lars, Lokki, Marja-Liisa, Mäntyselkä, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D, Moll, Frans L, Murray, Jeffrey C, Musk, Arthur W, Nieminen, Markku S, Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J, Oostra, Ben A, Palmer, Lyle J, Pankow, James S, Pasterkamp, Gerard, Pedersen, Nancy L, Pedersen, Oluf, Penninx, Brenda W, Perola, Markus, Peters, Annette, Polašek, Ozren, Pramstaller, Peter P, Psaty, Bruce M, Qi, Lu, Quertermous, Thomas, Raitakari, Olli T, Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M, Rioux, John D, Rivadeneira, Fernando, Rotter, Jerome I, Rudan, Igor, den Ruijter, Hester M, Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter EH, Shuldiner, Alan R, Sinisalo, Juha, Snieder, Harold, Sørensen, Thorkild IA, Spector, Tim D, Staessen, Jan A, Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, Verbeek, André LM, Vermeulen, Sita H, Viikari, Jorma S, Vitart, Veronique, Völzke, Henry, Vollenweider, Peter, Waeber, Gérard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J, Watkins, Hugh, Zeggini, Eleftheria, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Chakravarti, Aravinda, Clegg, Deborah J, Cupples, L Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E, Rao, DC, Abecasis, Goncalo R, Assimes, Themistocles L, Barroso, Inês, Berndt, Sonja I, Boehnke, Michael, Deloukas, Panos, Fox, Caroline S, Groop, Leif C, Hunter, David J, Ingelsson, Erik, Kaplan, Robert C, McCarthy, Mark I, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Hirschhorn, Joel N, Lindgren, Cecilia M, Heid, Iris M, North, Kari E, Borecki, Ingrid B, Kutalik, Zoltán, Loos, Ruth JF, Division of Statistical Genomics, Washington University School of Medicine, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Metabolic Science, MRC, Brown University, Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), King‘s College London, Groningen Bioinformatics Centre, GBB, University of Groningen [Groningen], University of Queensland [Brisbane], National Institut of Food Science and Technology, University of Agriculture, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of neurology, Leiden University Medical Center (LUMC), University of Washington [Seattle], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Limnology, Ecology, Department of Ecology and Evolutionary Biology, University of California, Core Genotyping Facility, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Cancer Epidemiology and Genetics, Institute of Health Sciences and Biocenter Oulu, University of Oulu, Department of Chemical Engineering Taiwan (DCET - NTHU), National Tsing Hua University [Hsinchu] (NTHU), University of Oxford [Oxford], Department of Epidemiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Departments of Epidemiology and Nutrition, Harvard School of Public Health, Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Department of Medical Sciences, Department of Educational Psychology and Counseling, National Taiwan Normal University (NTNU), Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE Genetics, deCODE genetics [Reykjavik], Interuniversity Cardiology Institute Netherlands, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Kidney Center, University Medical Center Groningen [Groningen] (UMCG), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], Medical Department III, Universität Leipzig [Leipzig], Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], GNS Science, Blackett Laboratory, Imperial College London, Medstar Research Institute, University of Rochester [USA], MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Dept Biochem & Mol Biol, Pennsylvania State University (Penn State), Penn State System-Penn State System, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Epidemiology, University Medical Centre Groningen, Unit for Molecular Epidemiology, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (KU), Faculty of Medicine, Institute of Public Health, Aalborg University [Denmark] (AAU), Department of Nutrition-Dietetics, Harokopio University of Athens, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, MRC National Survey of Health and Development, MRC Unit for Lifelong Health and Ageing, Department of Epidemiology and Public Health, University College of London [London] (UCL), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Research Center for Prevention and Health, Glostrup Hospital, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Cambridge Institute of Public Health, University of Cambridge [UK] (CAM), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Queensland Institute of Medical Research, Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Head of Medical Sequencing, Department of Biostatistics, University of Washington, Department of Chronic Disease Prevention, Molecular Epidemiology, Department of Genetics, Université Laval [Québec] (ULaval), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Department of Internal Medicine, Université de Lausanne (UNIL), Carl Gustav Carus University Hospital, Loughborough University, Genomics and Bioinformatics Platform, Fondazione Filarete, Department of Medicine, Surgery, and Dentistry, University of Milano, Medizinische Klinik II, Universität zu Lübeck [Lübeck], Department of Genomic Medicine, University of Manchester [Manchester], The Wellcome Trust Centre for Human Genetics [Oxford], National Institutes of Health [Bethesda] (NIH), Department of Nephrology, University Medical Center, University of Groningen, Helmholtz-Zentrum München (HZM), Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Genetics and Pathology, Department of child and adolescent psychiatry, Universität Duisburg-Essen [Essen], Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, Germany, Universität Regensburg (UR), Franz-Volhard-Centrum für Klinische Forschung, ECRC, Department of Clinical Physiology, University of Tampere [Finland]-Tampere University Hospital, Finnish Institute of Occupational Health of Helsinki, Department of Clinical Chemistry, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Oncology, University of Tampere Medical School, University of Tampere, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, Department of Medicine, Montreal, Developmental Brain and Behaviour Unit, University of Southampton, Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Centre for Bone and Arthritis Research, Institute of Medicine-University of Gothenburg (GU), Interdisciplinary Center for Psychiatric Epidemiology, Experimental Cardiology Laboratory, University Medical Center [Utrecht], Peter MacCallum Cancer Center, Faculty of Health Sciences, Aarhus University [Aarhus], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Department of Health Services, University of Washington, Group Health Research Institute, Group Health Cooperative, Department of Epidemiology, University of Washington, Department of Medicine, University of Washington, Cardiovascular Health Research Unit, University of Washington, The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital (TYKS), Erasmus Medical Centre, Cedars-Sinai Medical Center, Department of Pathological Biochemistry, Royal Infirmary, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Institute of Preventive Medicine, Copenhagen University Hospital-Bispebjerg and Frederiksberg Hospitals, Maastricht University [Maastricht], Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Epidemiology & Biostatistics, Radboud University Medical Center [Nijmegen], Institute for Community Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), MRC epidemiology Unit, Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Metabolic Disease Group, University of Cambridge Metabolic Research Laboratories, Department of Genetics and Biotechnology, Wellcome Trust, Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Department of Medical Genetics, Epidemiology Unit, Addenbrooke's Hospital-Medical Research Council (MRC), P30 AG010161/AG/NIA NIH HHS/United States, Psychiatry, Epidemiology and Data Science, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Other departments, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, RS: CARIM - R3 - Vascular biology, MUMC+: DA BV AIOS Radiologie (9), Epidemiologie, Orthopedie, Institute for Molecular Medicine Finland, Helsinki Collegium for Advanced Studies, Behavioural Sciences, University of Helsinki, Transplantation Laboratory, Medicum, Research Programs Unit, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Children's Hospital, Lastentautien yksikkö, Marja-Liisa Lokki / Principal Investigator, Kardiologian yksikkö, Leif Groop Research Group, Quantitative Genetics, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Ehret, Georg Benedikt, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universiteit Leiden-Universiteit Leiden, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of California (UC), University of Oxford, Lund University [Lund], Universität Leipzig, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (UCPH), Université de Lausanne = University of Lausanne (UNIL), Universität zu Lübeck = University of Lübeck [Lübeck], Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Gothenburg (GU)-Institute of Medicine, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Luan, Jian'an [0000-0003-3137-6337], Tyrer, Jonathan [0000-0003-3724-4757], Forouhi, Nita [0000-0002-5041-248X], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Luben, Robert [0000-0002-5088-6343], Ong, Kenneth [0000-0003-4689-7530], Johnson, Kathleen [0000-0002-6823-3252], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Apollo - University of Cambridge Repository, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Biochemistry, Surgery, Internal Medicine, Public Health, Medical Oncology, Pathology, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Clinical Genetics
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Male, Cancer Research, endocrine system diseases, Biological pathways, QH426-470, Genome, Body Mass Index, Body Size, Genetics (clinical), ddc:616, Genetics & Heredity, Sex Characteristics, Loci, MAGIC Consortium, Mass index, Age Factors, Chromosome Mapping, Middle Aged, Genealogy, Self-reported height, Peripheral-blood, Scale (social sciences), ICBP Consortium, Female, Life Sciences & Biomedicine, Medical Genetics, Research Article, arcOGEN Consortium, musculoskeletal diseases, Adult, European Continental Ancestry Group, Natural menopause, Aged, Body Size/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Biology, Body size, DIAGRAM Consortium, Age and sex, White People, Fat distribution, GLGC Consortium, 03 medical and health sciences, Life-course, Genetics, Weight-gain, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Medicinsk genetik, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0604 Genetics, Science & Technology, nutritional and metabolic diseases, Correction, 030104 developmental biology, GWAS meta-analysis, Global-BPGen Consortium, Common SNPS, CHARGE Consortium, 3111 Biomedicine, Developmental Biology
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR, Author Summary Adult body size and body shape differ substantially between men and women and change over time. More than 100 genetic variants that influence body mass index (measure of body size) or waist-to-hip ratio (measure of body shape) have been identified. While there is evidence that some genetic loci affect body shape differently in men than in women, little is known about whether genetic effects differ in older compared to younger adults, and whether such changes differ between men and women. Therefore, we conducted a systematic genome-wide search, including 114 studies (>320,000 individuals), to specifically identify genetic loci with age- and or sex-dependent effects on body size and shape. We identified 15 loci of which the effect on BMI was different in older compared to younger adults, whereas we found no evidence for loci with different effects in men compared to women. The opposite was seen for body shape as we identified 44 loci of which the effect on waist-to-hip ratio differed between men and women, but no difference between younger and older adults were observed. Our observations may provide new insights into the biology that underlies weight change with age or the sexual dimorphism of body shape.
Published: 2014

14. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies

Author: Inês Barroso, Naveed Sattar, Claudia Langenberg, Nicholas J. Wareham, Kay-Tee Khaw, Roman Pfister, Robert Luben, Veikko Salomaa, Paul Welsh, Aline Meirhaeghe, Stephen J. Sharp, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Department III of Internal Medicine, Heart Centre of the University of Cologne, Department of Public Health and Primary Care, Institute of Public Health, Division of Cardiovascular and Medical Sciences, University of Glasgow, Metabolic Disease Group, The Wellcome Trust Sanger Institute [Cambridge], University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, University of Cambridge [UK] (CAM), Department of Pathological Biochemistry, Royal Infirmary, Medical Research Council, Institute of Metabolic Science-Epidemiology Unit, Cambridgeshire, Ely, ADDITION, EPIC-Norfolk, and the Norfolk Diabetes studies were funded by the MRC with support from NHS Research & Development and the Wellcome Trust. RP received grants from Koeln Fortune and Marga- und Walter-Boll Stiftung. IB acknowledges funding from Wellcome Trust grant 077016/Z/05/Z and United Kingdom NIHR Cambridge Biomedical Research Centre and the MRC Centre for Obesity and Related Metabolic Diseases. PW is supported by BHF fellowship grant FS/10/005/28147. NT-pro-BNP determination in FINRISK97 was done as a part of the MORGAM Biomarker Study funded in part by the Medical Research Council London (G0601463, identification no. 80983) and Roche Diagnostics provided test reagents. VS was supported by the Academy of Finland, grant no 129494., and Autard, Delphine
Subjects: Male, medicine.medical_specialty, Inverse Association, Genotype, endocrine system diseases, Epidemiology, Population, Type 2 diabetes, 030204 cardiovascular system & hematology, Risk Assessment, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Internal medicine, Natriuretic Peptide, Brain, Mendelian randomization, Humans, Medicine, Prospective Studies, education, Alleles, Aged, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, education.field_of_study, business.industry, Hazard ratio, Case-control study, Genetic Variation, General Medicine, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Endocrinology, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Genetic Epidemiology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index, human activities, Research Article
Abstract: Using mendelian randomization, Roman Pfister and colleagues demonstrate a potentially causal link between low levels of B-type natriuretic peptide (BNP), a hormone released by damaged hearts, and the development of type 2 diabetes., Background Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. Methods and Findings We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%–36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91–0.97) was similar to that expected (0.96, 0.93–0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74–0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15–0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. Conclusions Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions. Please see later in the article for the Editors' Summary, Editors' Summary Background Worldwide, nearly 250 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous amounts of sugar (glucose) in the blood. Blood sugar levels are normally controlled by insulin, a hormone that the pancreas releases after meals (digestion of food produces glucose). In people with type 2 diabetes (the most common form of diabetes), blood sugar control fails because the fat and muscle cells that usually respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. The long-term complications of diabetes, which include kidney failure and an increased risk of cardiovascular problems such as heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes. Why Was This Study Done? Because the causes of type 2 diabetes are poorly understood, it is hard to devise ways to prevent the condition. Recently, B-type natriuretic peptide (BNP, a hormone released by damaged hearts) has been implicated in type 2 diabetes development in cross-sectional studies (investigations in which data are collected at a single time point from a population to look for associations between an illness and potential risk factors). Although these studies suggest that high levels of BNP may protect against type 2 diabetes, they cannot prove a causal link between BNP levels and diabetes because the study participants with low BNP levels may share some another unknown factor (a confounding factor) that is the real cause of both diabetes and altered BNP levels. Here, the researchers use an approach called “Mendelian randomization” to examine whether reduced BNP levels contribute to causing type 2 diabetes. It is known that a common genetic variant (rs198389) within the genome region that encodes BNP is associated with a reduced risk of type 2 diabetes. Because gene variants are inherited randomly, they are not subject to confounding. So, by investigating the association between BNP gene variants that alter NT-pro-BNP (a molecule created when BNP is being produced) levels and the development of type 2 diabetes, the researchers can discover whether BNP is causally involved in this chronic condition. What Did the Researchers Do and Find? The researchers analyzed the association between blood levels of NT-pro-BNP at baseline in 440 participants of the EPIC-Norfolk study (a prospective population-based study of lifestyle factors and the risk of chronic diseases) who subsequently developed diabetes and in 740 participants who did not develop diabetes. In this prospective case-cohort study, the risk of developing type 2 diabetes was associated with lower NT-pro-BNP levels. They also genotyped (sequenced) rs198389 in the participants of three case-control studies of type 2 diabetes (studies in which potential risk factors for type 2 diabetes were examined in people with type 2 diabetes and matched controls living in the East of England), and combined these results with those of eight similar published case-control studies. Finally, the researchers showed that the association between rs198389 and type 2 diabetes measured in the case-control studies was similar to the expected association calculated from the association between NT-pro-BNP level and type 2 diabetes obtained from the prospective case-cohort study and the association between rs198389 and BNP levels obtained from the EPIC-Norfolk study and other published studies. What Do These Findings Mean? The results of this Mendelian randomization study provide evidence for a causal, protective role of the BNP hormone system in the development of type 2 diabetes. That is, these findings suggest that low levels of BNP are partly responsible for the development of type 2 diabetes. Because the participants in all the individual studies included in this analysis were of European descent, these findings may not be generalizable to other ethnicities. Moreover, they provide no explanation of how alterations in the BNP hormone system might affect the development of type 2 diabetes. Nevertheless, the demonstration of a causal link between the BNP hormone system and type 2 diabetes suggests that BNP may be a potential target for interventions designed to prevent type 2 diabetes, particularly since the feasibility of altering BNP levels with drugs has already been proven in patients with cardiovascular disease. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001112. The International Diabetes Federation provides information about all aspects of diabetes The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health-care professionals, and the general public (in English and Spanish) The UK National Health Service Choices website also provides information for patients and carers about type 2 diabetes and includes people's stories about diabetes MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish) Wikipedia has pages on BNP and on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) The charity Healthtalkonline has interviews with people about their experiences of diabetes; the charity Diabetes UK has a further selection of stories from people with diabetes
Published: 2011

15. OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions

Author: António L. Palmeira, Thorkild I. A. Sørensen, Martin Neovius, Martine Laville, Mikael Rydén, Andrea Natali, Maud Alligier, Romain Barrès, Kristina Campbell, David Jacobi, I. Sadaf Farooqi, Jean-Michel Oppert, Helen M. Roche, André Scheen, Karine Clément, Ellen E. Blaak, Yves Boirie, Gijs H. Goossens, Jason C.G. Halford, Luc Tappy, Nathalie Farpour-Lambert, Hannele Yki-Järvinen, Uberto Pagotto, Chantal Simon, Jörg Hager, Jildau Bouwman, Paul Brunault, Gema Frühbeck, Dominique Langin, Olivier Ziegler, Chantal Julia, Hans Hauner, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), University of Copenhagen = Københavns Universitet (KU), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], CHU Clermont-Ferrand, Netherlands Organization for Applied Scientific Research (TNO), TNO Science and Industry, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), KC Microbiome Communications Group, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University of Cambridge [UK] (CAM), Université de Genève (UNIGE), Geneva University Hospitals and Geneva University, Clínica Universidad de Navarra [Pamplona], Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], University of Liverpool, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Klinikums rechts der Isar, Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pisa - Università di Pisa, Karolinska Institutet [Stockholm], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Alma Mater Studiorum University of Bologna (UNIBO), Université de Lisbonne, University College Dublin [Dublin] (UCD), Centre Hospitalier Universitaire de Liège (CHU-Liège), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lausanne (UNIL), Minerva Foundation Institute for Medical Research, University of Helsinki, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Joint Programming Initiative Heathy Diet for Healthy Life, Alligier M., Barres R., Blaak E.E., Boirie Y., Bouwman J., Brunault P., Campbell K., Clement K., Farooqi I.S., Farpour-Lambert N.J., Fruhbeck G., Goossens G.H., Hager J., Halford J.C.G., Hauner H., Jacobi D., Julia C., Langin D., Natali A., Neovius M., Oppert J.M., Pagotto U., Palmeira A.L., Roche H., Ryden M., Scheen A.J., Simon C., Sorensen T.I.A., Tappy L., Yki-Jarvinen H., Ziegler O., Laville M., FCRIN/FORCE Network, Centre de Recherche en Nutrition Humaine Rhône-Alpes, Novo Nordisk, Department of Human Biology, Maastricht University Medical Center (MUMC), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Nutrition clinique, Centre Hospitalier Universitaire Gabriel Montpied, TNO,Netherlands Organisation for Applied Scientific Research, UMR U 1253, Université de Tours, Nutrition et obésité : approches systémiques, Sorbonne Université, Wellcome-MRC Institute of Metabolic Science and NIHR Biomedical Research Centre, University of Cambridge, Service of Therapeutic Education for Chronic Diseases, Department of Community Health, Primary Care and Emergency, Geneva University Hospitals, Department of Endocrinology and Nutrition, Navarra Public Health Institute, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición - Biomedical Research Center in Red-Physiopathology of Obesity and Nutrition (CIBEROBN), University of Navarra, University of Cape Town, Metabolic Phenotyping, Nestlé Institute of Health Sciences, Psychological Sciences, University of Liverpool (University of Liverpool), Institut für Ernährungsmedizin des Klinikums Rechts der Isar, Technical University of Munich (TUM), Institut du Thorax, Centre Hospitalier Universitaire de Nantes, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université Toulouse III - Paul Sabatier, Centre Hospitalier Universitaire de Toulouse, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Department of Medicine (Solna), Nutrition, Institut de Cardiométabolisme et Nutrition (ICAN), CHU Pitié-Salpêtrière [APHP], Department of Medical and Surgical Sciences, Universita degli Studi di Padova, CIPER, PANO-SR, Faculty of Human Kinetics, University of Lisbon, UCD Institute of Food and Health, University College Dublin (UCD), Department of Medicine, The University of Sydney, Diabètes, Nutrition et maladies métaboliques, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Physiologie, Université de Picardie Jules Verne (UPJV), Helsinki University Central Hospital, Endocrinologie, Diabetes et Nutrition, Hôpital Brabois, Maastricht University [Maastricht]-Maastricht University [Maastricht], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ProdInra, Archive Ouverte, Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Université de Genève = University of Geneva (UNIGE), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lausanne = University of Lausanne (UNIL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, HUS Internal Medicine and Rehabilitation, Humane Biologie, and RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health
Subjects: 0301 basic medicine, Research design, Gerontology, Health (social science), Psychological intervention, Choice Behavior, 0302 clinical medicine, QUALITY-OF-LIFE, OBSTRUCTIVE SLEEP-APNEA, Medicine, Medical History Taking, lcsh:RC620-627, Interventions, METABOLIC SYNDROME, Randomized Controlled Trials as Topic, ddc:616, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Precision medicine, Prognosis, C-REACTIVE PROTEIN, 3. Good health, Europe, lcsh:Nutritional diseases. Deficiency diseases, CARDIOVASCULAR-DISEASE, Research Design, Variable, lcsh:Nutrition. Foods and food supply, Human, Prognosi, education, WEIGHT-LOSS, lcsh:TX341-641, Intervention, 030209 endocrinology & metabolism, GASTRIC BYPASS-SURGERY, Guidelines, Patient care, 03 medical and health sciences, Variables, Physiology (medical), Humans, CORONARY-HEART-DISEASE, Obesity, Expert Testimony, Core set, 030109 nutrition & dietetics, business.industry, Stratification, medicine.disease, Diet, BODY-MASS INDEX, Clinical trial, PHYSICAL-ACTIVITY, Biological Variation, Population, 3121 General medicine, internal medicine and other clinical medicine, Metabolic syndrome, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes. © 2020 The Author(s) Published by S. Karger AG, Basel.
Published: 2020

16. Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity

Author: I. Sadaf Farooqi, Marcella Ma, Ilona Zvetkova, Brian Y.H. Lam, Irene Cimino, Luca Fagnocchi, Pierre Larraufie, Y. C. Loraine Tung, Giles S.H. Yeo, Debra Rimmington, J. Andrew Pospisilik, Frank Reimann, Richard G. Kay, Stephen O'Rahilly, Vladimir Saudek, Anthony P. Coll, Samuel Virtue, Fiona M. Gribble, Katherine Lawler, Antonio Vidal-Puig, Wellcome Trust-MRC Institute of Metabolic Science, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Van Andel Institute [Grand Rapids], Cimino, Irene [0000-0003-1397-5408], Farooqi, Ismaa [0000-0001-7609-3504], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], Coll, Anthony [0000-0003-2594-7463], and Apollo - University of Cambridge Repository
Subjects: Male, Molecular biology, Physiology, 631/208, Eating, Mice, 0302 clinical medicine, Gene expression, 631/443, 2. Zero hunger, Mice, Knockout, 0303 health sciences, Multidisciplinary, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Phenotype, Null allele, Medicine, Female, 631/378, 631/337, medicine.medical_specialty, Science, Nerve Tissue Proteins, Biology, Diet, High-Fat, Article, 03 medical and health sciences, Internal medicine, medicine, Genetics, Animals, Obesity, 030304 developmental biology, Gene Expression Profiling, Body Weight, Wild type, Membrane Proteins, medicine.disease, Sexual dimorphism, Mice, Inbred C57BL, Endocrinology, Neuronatin, Genomic imprinting, Energy Metabolism, 030217 neurology & neurosurgery, Biomarkers, Neuroscience
Abstract: Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat+/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat+/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat+/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat+/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat+/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat+/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.
Published: 2021

17. Stimulation of motilin secretion by bile, free fatty acids, and acidification in human duodenal organoids

Author: Deborah A. Goldspink, Van B. Lu, Christopher A. Smith, Pierre Larraufie, Richard G. Kay, Fiona M. Gribble, Rachel E. Foreman, Frank Reimann, Amy L. George, Emily L. Miedzybrodzka, Wellcome Trust-MRC Institute of Metabolic Science (IMS), Kay, Richard [0000-0002-3827-8687], Reimann, Frank [0000-0001-9399-6377], Gribble, Fiona [0000-0002-4232-2898], and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, Duodenum, chemistry.chemical_element, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Fatty Acids, Nonesterified, Calcium, Motilin, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Organoid, Bile, Humans, Secretion, Receptor, Molecular Biology, Cells, Cultured, Human intestinal organoids, 030304 developmental biology, Cholecystokinin, 0303 health sciences, digestive, oral, and skin physiology, Cell Biology, Hydrogen-Ion Concentration, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, RC31-1245, G protein-coupled bile acid receptor, Enteroendocrine hormones, Organoids, Monoacylglycerol lipase, Endocrinology, chemistry, Original Article, 030211 gastroenterology & hepatology, hormones, hormone substitutes, and hormone antagonists
Abstract: Objective Motilin is a proximal small intestinal hormone with roles in gastrointestinal motility, gallbladder emptying, and hunger initiation. In vivo motilin release is stimulated by fats, bile, and duodenal acidification but the underlying molecular mechanisms of motilin secretion remain poorly understood. This study aimed to establish the key signaling pathways involved in the regulation of secretion from human motilin-expressing M-cells. Methods Human duodenal organoids were CRISPR-Cas9 modified to express the fluorescent protein Venus or the Ca2+ sensor GCaMP7s under control of the endogenous motilin promoter. This enabled the identification and purification of M-cells for bulk RNA sequencing, peptidomics, calcium imaging, and electrophysiology. Motilin secretion from 2D organoid-derived cultures was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in parallel with other gut hormones. Results Human duodenal M-cells synthesize active forms of motilin and acyl-ghrelin in organoid culture, and also co-express cholecystokinin (CCK). Activation of the bile acid receptor GPBAR1 stimulated a 3.4-fold increase in motilin secretion and increased action potential firing. Agonists of the long-chain fatty acid receptor FFA1 and monoacylglycerol receptor GPR119 stimulated secretion by 2.4-fold and 1.5-fold, respectively. Acidification (pH 5.0) was a potent stimulus of M-cell calcium elevation and electrical activity, an effect attributable to acid-sensing ion channels, and a modest inducer of motilin release. Conclusions This study presents the first in-depth transcriptomic and functional characterization of human duodenal motilin-expressing cells. We identify several receptors important for the postprandial and interdigestive regulation of motilin release., Highlights • Mechanisms of motilin secretion were assessed in a new human duodenal organoid model. • RNA sequencing identified ion channels and receptors involved in M-cell activity. • M-cells fired action potentials similar to those in other enteroendocrine cell types. • Motilin release was triggered by low pH, bile, and free fatty acid receptor-1 ligands. • Low pH depolarized M-cells and increased calcium through acid-sensing ion channels (ASIC). Image 1
Published: 2021

18. The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1

Author: Claire L Meek, Richard G. Kay, Sam G Galvin, Pierre Larraufie, Rachel E. Foreman, Frank Reimann, Fiona M. Gribble, Peter Ravn, Emma K. Biggs, Lutz Jermutus, Wellcome Trust-MRC Institute of Metabolic Science, Gribble, Fiona M [0000-0002-4232-2898], and Apollo - University of Cambridge Repository
Subjects: medicine.medical_specialty, endocrine system, endocrine system diseases, medicine.medical_treatment, Prohormone, 030209 endocrinology & metabolism, Biochemistry, Glucagon, Article, Islets of Langerhans, Mice, 03 medical and health sciences, 0302 clinical medicine, Glucagon-Like Peptide 1, Internal medicine, medicine, Animals, Humans, Insulin, Obesity, Peptidomics, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Proinsulin, 0303 health sciences, geography, Delta cell, geography.geographical_feature_category, pancreatic islets, Mass spectrometry, Chemistry, Pancreatic islets, Type 2 diabetes, General Chemistry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Islet, Glucagon-like peptide-1, 3. Good health, Endocrinology, medicine.anatomical_structure, Diabetes Mellitus, Type 2, medicine.drug
Abstract: To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with type 2 diabetes. Islets were obtained from healthy and type 2 diabetic human donors, and mice on chow or high fat diet. All major islet hormones were detected in lysed islets as well as numerous peptides from vesicular proteins including granins and processing enzymes. Glucose-dependent insulinotropic peptide (GIP) was not detectable. High fat diet modestly increased islet content of proinsulin-derived peptides in mice. Human diabetic islets contained increased content of proglucagon-derived peptides at the expense of insulin, but no evident prohormone processing defects. Diabetic plasma, however, contained increased ratios of proinsulin and des-31,32-proinsulin to insulin. Active GLP-1 was detectable in human and mouse islets but 100-1000-fold less abundant than glucagon. LC-MS offers advantages over antibody-based approaches for identifying exact peptide sequences, and revealed a shift toward islet insulin production in high fat fed mice, and toward proglucagon production in type 2 diabetes, with no evidence of systematic defective prohormone processing.
Published: 2021

19. Ghrelin Does Not Directly Stimulate Secretion of Glucagon-like Peptide-1

Author: Pierre Larraufie, Jens Otto Lunde Jørgensen, Fiona M. Gribble, Frank Reimann, Sara L. Jepsen, Esben Thyssen Vestergaard, Rune E. Kuhre, Jens J. Holst, Metabolic Research Laboratories, Institute of Metabolic Science, and University of Cambridge [UK] (CAM)
Subjects: Male, SURGERY, Denmark, Endocrinology, Diabetes and Metabolism, Receptor expression, Clinical Biochemistry, Biochemistry, Placebos, Mice, L Cells, 0302 clinical medicine, Endocrinology, Glucagon-Like Peptide 1, GLP-1 SECRETION, Intestinal Mucosa, Receptor, Cells, Cultured, media_common, 0303 health sciences, Cross-Over Studies, Secretory Pathway, Chemistry, digestive, oral, and skin physiology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Glucagon-like peptide-1, Ghrelin, Growth hormone secretion, Up-Regulation, 3. Good health, Intestines, Gastrointestinal hormone, GLUCOSE-ABSORPTION, HORMONES, Administration, Intravenous, MEAL, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, media_common.quotation_subject, 030209 endocrinology & metabolism, INSULIN-SECRETION, Hypopituitarism, MECHANISMS, 03 medical and health sciences, Double-Blind Method, Internal medicine, medicine, Animals, Humans, Clinical Research Articles, Aged, 030304 developmental biology, RECEPTOR, Biochemistry (medical), Appetite, Mice, Inbred C57BL, CELLS, WEIGHT, Hormone
Abstract: Context The gastrointestinal hormone ghrelin stimulates growth hormone secretion and appetite, but recent studies indicate that ghrelin also stimulates the secretion of the appetite-inhibiting and insulinotropic hormone glucagon-like peptide-1 (GLP-1). Objective To investigate the putative effect of ghrelin on GLP-1 secretion in vivo and in vitro. Subjects and Methods A randomized placebo-controlled crossover study was performed in eight hypopituitary subjects. Ghrelin or saline was infused intravenously (1 pmol/min × kg) after collection of baseline sample (0 min), and blood was subsequently collected at time 30, 60, 90, and 120 minutes. Mouse small intestine was perfused (n = 6) and GLP-1 output from perfused mouse small intestine was investigated in response to vascular ghrelin administration in the presence and absence of a simultaneous luminal glucose stimulus. Ghrelin receptor expression was quantified in human (n = 11) and mouse L-cells (n = 3) by RNA sequencing and RT-qPCR, respectively. Results Ghrelin did not affect GLP-1 secretion in humans (area under the curve [AUC; 0–120 min]: ghrelin infusion = 1.37 ± 0.05 min × nmol vs. saline infusion = 1.40 ± 0.06 min × nmol [P = 0.63]), but induced peripheral insulin resistance. Likewise, ghrelin did not stimulate GLP-1 secretion from the perfused mouse small intestine model (mean outputs during baseline/ghrelin infusion = 19.3 ± 1.6/25.5 ± 2.0 fmol/min, n = 6, P = 0.16), whereas glucose-dependent insulinotropic polypeptide administration, used as a positive control, doubled GLP-1 secretion (P < 0.001). Intraluminal glucose increased GLP-1 secretion by 4-fold (P < 0.001), which was not potentiated by ghrelin. Finally, gene expression of the ghrelin receptor was undetectable in mouse L-cells and marginal in human L-cells. Conclusions Ghrelin does not interact directly with the L-cell and does not directly affect GLP-1 secretion.
Published: 2019

20. Characterisation of proguanylin expressing cells in the intestine – evidence for constitutive luminal secretion

Author: Claire L Meek, Geoffrey P. Roberts, Tristan J Vaughan, Richard G. Kay, Florent Serge Dye, Deborah A. Goldspink, Benjamin G. Challis, Pierre Larraufie, Maria A T Groves, Fiona M. Gribble, Frank Reimann, Franco Ferraro, Stephen J. Middleton, Juraj Rievaj, Richard H. Hardwick, Jennifer L. Percival-Alwyn, Tamana Darwish, Stephen O'Rahilly, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge [UK] (CAM), O’Rahilly, Stephen [0000-0003-2199-4449], Reimann, Frank [0000-0001-9399-6377], Apollo - University of Cambridge Repository, and O'Rahilly, Stephen [0000-0003-2199-4449]
Subjects: 0301 basic medicine, Genetically modified mouse, Guanylin, lcsh:Medicine, 96/31, Article, 692/4020/198, 38/91, 96/95, Gastrointestinal Hormones, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, 692/163/2778, Organoid, medicine, Humans, Secretion, Intestinal Mucosa, Protein Precursors, Natriuretic Peptides, lcsh:Science, 14/35, Multidisciplinary, Ussing chamber, Chemistry, 82/58, lcsh:R, 64/110, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Golgi apparatus, Small intestine, 3. Good health, Cell biology, Transplantation, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Preclinical research, 030220 oncology & carcinogenesis, 14/63, symbols, lcsh:Q, 82/1
Abstract: Guanylin, a peptide implicated in regulation of intestinal fluid secretion, is expressed in the mucosa, but the exact cellular origin remains controversial. In a new transgenic mouse model fluorescent reporter protein expression driven by the proguanylin promoter was observed throughout the small intestine and colon in goblet and Paneth(-like) cells and, except in duodenum, in mature enterocytes. In Ussing chamber experiments employing both human and mouse intestinal tissue, proguanylin was released predominantly in the luminal direction. Measurements of proguanylin expression and secretion in cell lines and organoids indicated that secretion is largely constitutive and requires ER to Golgi transport but was not acutely regulated by salt or other stimuli. Using a newly-developed proguanylin assay, we found plasma levels to be raised in humans after total gastrectomy or intestinal transplantation, but largely unresponsive to nutrient ingestion. By LC-MS/MS we identified processed forms in tissue and luminal extracts, but in plasma we only detected full-length proguanylin. Our transgenic approach provides information about the cellular origins of proguanylin, complementing previous immunohistochemical and in-situ hybridisation results. The identification of processed forms of proguanylin in the intestinal lumen but not in plasma supports the notion that the primary site of action is the gut itself.
Published: 2019

21. Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery

Author: Kathleen Davy, Andrew B. Leiter, Audrey Melvin, Anne K. McGavigan, Joyce Li, Richard H. Hardwick, Geoffrey P. Roberts, Emma K. Biggs, Richard G. Kay, Giles S.H. Yeo, Peter Ravn, Fiona M. Gribble, David C. Hornigold, Pierre Larraufie, Frank Reimann, Wellcome Trust-MRC Institute of Metabolic Science, Larraufie, Pierre [0000-0001-7718-6200], Kay, Richard [0000-0002-3827-8687], Yeo, Giles [0000-0001-8823-3615], Reimann, Frank [0000-0001-9399-6377], Gribble, Fiona [0000-0002-4232-2898], and Apollo - University of Cambridge Repository
Subjects: Male, gut hormones, medicine.medical_treatment, Enteroendocrine cell, Type 2 diabetes, Mice, transcriptomics, Weight loss, intestinal transit, Glucagon-Like Peptide 1, Insulin Secretion, Glucose homeostasis, Homeostasis, Insulin, Postoperative Period, Intestinal Mucosa, 050207 economics, Receptor, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, mass spectrometry, 050208 finance, 05 social sciences, digestive, oral, and skin physiology, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Female, medicine.symptom, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, endocrine system, bariatric surgery, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, 0502 economics and business, medicine, Animals, Hypoglycemic Agents, Humans, Peptide YY, Secretion, Obesity, enteroendocrine cells, business.industry, peptidomics, medicine.disease, Peptide Fragments, Surgery, Mice, Inbred C57BL, Glucose, lcsh:Biology (General), Transcriptome, business, GLP-1
Abstract: Summary Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion., Graphical Abstract, Highlights • Increased postprandial GLP-1 triggers higher insulin levels after bariatric surgery • Bariatric surgery does not change enteroendocrine cell identity or hormone content • Increased nutrient flow to the distal gut after surgery enhances GLP-1 secretion, Bariatric surgery is associated with enhanced postprandial gut hormone release, particularly of GLP-1, which increases insulin secretion and glucose clearance. Larraufie et al. show that higher gut hormone levels are due not to changes in enteroendocrine cell characteristics or tissue hormone content but to altered flow of nutrients that stimulates more distal enteroendocrine cells.
Published: 2019

22. Nutritional and developmental programming effects of insulin

Author: Laura Dearden, Susan E. Ozanne, Sebastien G. Bouret, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Wellcome Trust-MRC Institute of Metabolic Science (IMS), Lille Neurosciences & Cognition - U 1172 (LilNCog), Bouret, Sebastien G [0000-0002-4174-9769], Apollo - University of Cambridge Repository, and Bouret, Sebastien
Subjects: obesity, medicine.medical_specialty, endocrine system diseases, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Disease, Type 2 diabetes, Overweight, Bioinformatics, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, developmental programming, Diabetes mellitus, Internal medicine, medicine, hypothalamus, ComputingMilieux_MISCELLANEOUS, diabetes, hormones, Endocrine and Autonomic Systems, business.industry, Insulin, nutritional and metabolic diseases, medicine.disease, Obesity, 3. Good health, [SDV] Life Sciences [q-bio], Gestational diabetes, medicine.symptom, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Hormone
Abstract: International audience; The discovery of insulin in 1921 was a major breakthrough in medicine and for therapy in patients with diabetes. The dramatic rise in the prevalence of overweight and obesity has been tightly linked to an increased prevalence of gestational diabetes mellitus (GDM), which poses major health concerns. Babies born to GDM mothers are more likely to develop obesity, type 2 diabetes and cardiovascular disease later in life. Evidence accumulated during the past two decades has revealed that high levels insulin, such as those observed during GDM, can have a widespread effect on the development and function of a variety of organs. This review summarises our current knowledge on the role of insulin in the placenta, cardiovascular system and brain during critical periods of development, as well as how it can contribute to lifelong metabolic regulation. We also discuss possible intervention strategies to ameliorate and hopefully reverse the developmental defects associated with obesity and GDM.
Published: 2021

23. Peptidomics of enteroendocrine cells and characterisation of potential effects of a novel preprogastrin derived-peptide on glucose tolerance in lean mice

Author: Anne K. McGavigan, Van B. Lu, Laura Sheldrake, Elise Bernard, Helen Brant, Sam G Galvin, Haidee Pitt, Pierre Larraufie, David Baker, Frank Reimann, Elisabeth O’Flaherty, Carina Ämmälä, Lutz Jermutus, John Hood, Shannon Conder, Geoffrey P. Roberts, Dawn Atherton-Kemp, Richard G. Kay, Fiona M. Gribble, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge [UK] (CAM), Galvin, Sam [0000-0001-5910-9471], Kay, Richard [0000-0002-3827-8687], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Proteome, Physiology, Enteroendocrine cell, Peptide, Biochemistry, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, 0302 clinical medicine, Endocrinology, Biosynthesis, Thinness, In vivo, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gastrins, Animals, Humans, Protein Precursors, Peptidomics, Gene, Cells, Cultured, chemistry.chemical_classification, Enteroendocrine cells, biology, Mass spectrometry, Chemistry, Progastrin, Chromogranin A, Prohormones, Glucose Tolerance Test, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, In vitro, 3. Good health, Gastrointestinal Tract, 030104 developmental biology, Glucose, Granins, Models, Animal, biology.protein, Peptides, 030217 neurology & neurosurgery, Hormone
Abstract: Highlights • A peptidomic analysis of the human and mouse gastrointestinal tract was performed. • High fat feeding reduced the content of GCG, PYY and INSL5 in the distal colon. • Several interesting novel peptides were synthesised for in vivo characterisation. • A novel product of progastrin modestly improved glucose tolerance in lean mice., Objectives To analyse the peptidomics of mouse enteroendocrine cells (EECs) and human gastrointestinal (GI) tissue and identify novel gut derived peptides. Methods High resolution nano-flow liquid chromatography mass spectrometry (LC–MS/MS) was performed on (i) flow-cytometry purified NeuroD1 positive cells from mouse and homogenised human intestinal biopsies, (ii) supernatants from primary murine intestinal cultures, (iii) intestinal homogenates from mice fed high fat diet. Candidate bioactive peptides were selected on the basis of species conservation, high expression/biosynthesis in EECs and evidence of regulated secretionin vitro. Candidate novel gut-derived peptides were chronically administered to mice to assess effects on food intake and glucose tolerance. Results A large number of peptide fragments were identified from human and mouse, including known full-length gut hormones and enzymatic degradation products. EEC-specific peptides were largely from vesicular proteins, particularly prohormones, granins and processing enzymes, of which several exhibited regulated secretion in vitro. No regulated peptides were identified from previously unknown genes. High fat feeding particularly affected the distal colon, resulting in reduced peptide levels from GCG, PYY and INSL5. Of the two candidate novel peptides tested in vivo, a peptide from Chromogranin A (ChgA 435−462a) had no measurable effect, but a progastrin-derived peptide (Gast p59−79), modestly improved glucose tolerance in lean mice. Conclusion LC–MS/MS peptidomic analysis of murine EECs and human GI tissue identified the spectrum of peptides produced by EECs, including a potential novel gut hormone, Gast p59−79, with minor effects on glucose tolerance.
Published: 2021

24. Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells

Author: Benjamin Jenkins, Debra Rimmington, Brian Y.H. Lam, Pierre Larraufie, Marcella Ma, Frank Reimann, Deborah A. Goldspink, Anthony P. Coll, Tamana Darwish, Cheryl A. Brighton, Stephen O'Rahilly, Albert Koulman, Irene Cimino, Fiona M. Gribble, Ming Yang, Apollo - University of Cambridge Repository, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge [UK] (CAM), Cimino, Irene [0000-0003-1397-5408], Koulman, Albert [0000-0001-9998-051X], Coll, Anthony [0000-0003-2594-7463], O'Rahilly, Stephen [0000-0003-2199-4449], Reimann, Frank [0000-0001-9399-6377], and Gribble, Fiona [0000-0002-4232-2898]
Subjects: Male, 0301 basic medicine, endocrine system diseases, Physiology, [SDV]Life Sciences [q-bio], Glucose uptake, Glucose Transport Proteins, Facilitative, Oxidative Phosphorylation, Mice, Endocrinology, 0302 clinical medicine, Glycolysis, 631/443, 692/163, Intestinal Mucosa, Cells, Cultured, Multidisciplinary, SLC5A1, Molecular medicine, biology, Chemistry, digestive, oral, and skin physiology, Gastroenterology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Metformin, Mitochondria, 3. Good health, Medicine, medicine.drug, Cell biology, medicine.medical_specialty, Growth Differentiation Factor 15, Science, 692/308, Cell Respiration, 692/4020, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Medical research, Downregulation and upregulation, Internal medicine, Diabetes mellitus, medicine, Animals, Gene Expression Profiling, Computational Biology, nutritional and metabolic diseases, Biological Transport, medicine.disease, 692/4017, Glucose, 030104 developmental biology, biology.protein, GLUT2, GLUT1, 631/80, Transcriptome
Abstract: Even though metformin is widely used to treat type2 diabetes, reducing glycaemia and body weight, the mechanisms of action are still elusive. Recent studies have identified the gastrointestinal tract as an important site of action. Here we used intestinal organoids to explore the effects of metformin on intestinal cell physiology. Bulk RNA-sequencing analysis identified changes in hexose metabolism pathways, particularly glycolytic genes. Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates. Metformin caused mitochondrial dysfunction and metformin’s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss. Gene expression changes elicited by metformin were replicated in 3D apical-out organoids and distal small intestines of metformin treated mice. We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction. This may explain the effects of metformin on intestinal glucose utilisation and food balance.
Published: 2021

25. Organoid Sample Preparation and Extraction for LC-MS Peptidomics

Author: Fiona M. Gribble, Amy L. George, Emily L. Miedzybrodzka, Rachel E. Foreman, Pierre Larraufie, Frank Reimann, Richard G. Kay, Deborah A. Goldspink, Sam G Galvin, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge [UK] (CAM), Galvin, Sam [0000-0001-5910-9471], Reimann, Frank [0000-0001-9399-6377], Gribble, Fiona [0000-0002-4232-2898], Kay, Richard [0000-0002-3827-8687], and Apollo - University of Cambridge Repository
Subjects: Proteomics, Primary culture, [SDV]Life Sciences [q-bio], Enteroendocrine cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, General Biochemistry, Genetics and Molecular Biology, Mass Spectrometry, 03 medical and health sciences, 0302 clinical medicine, Liquid chromatography–mass spectrometry, Tandem Mass Spectrometry, Organoid, Protocol, Humans, Sample preparation, Amino Acid Sequence, lcsh:Science (General), 030304 developmental biology, 0303 health sciences, Chromatography, General Immunology and Microbiology, Chemistry, General Neuroscience, Limiting, Flow Cytometry, 3. Good health, Organoids, Peptides, 030217 neurology & neurosurgery, lcsh:Q1-390, Chromatography, Liquid
Abstract: Summary This protocol describes the peptidomic analysis of organoid lysates, FACS-purified cell populations, and 2D culture secretions by liquid chromatography mass spectrometry (LC-MS). Currently, most peptides are quantified by ELISA, limiting the peptides that can be studied. However, an LC-MS-based approach allows more peptides to be monitored. Our group has previously used LC-MS for tissue peptidomics and secretion of enteroendocrine peptides from primary culture. Now, we extend the use to organoid models. For complete details on the use and execution of this protocol, please refer to Goldspink et al. (2020)., Graphical Abstract, Highlights • Preparing organoid cultures, secretions, and FAC-sorted cells for peptidomics • An established pipeline covering peptide extraction, LC-MS, and data analysis • Unambiguous detection of closely related peptide hormones • Semi-quantitative analysis of secreted peptides from stimulated organoid cultures, This protocol describes the peptidomic analysis of organoid lysates, FACS-purified cell populations, and 2D culture secretions by liquid chromatography mass spectrometry (LC-MS). Currently, most peptides are quantified by ELISA, limiting the peptides that can be studied. However, an LC-MS-based approach allows more peptides to be monitored. Our group has previously used LC-MS for tissue peptidomics and secretion of enteroendocrine peptides from primary culture. Now, we extend the use to organoid models.
Published: 2020

26. Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine

Author: Kirstine N. Bojsen-Møller, Fiona M. Gribble, Sten Madsbad, Ida M. Modvig, Nicolai J. Wewer Albrechtsen, Bolette Hartmann, Daniel B. Andersen, Cathrine Ørskov, Rune E. Kuhre, Pierre Larraufie, Frank Reimann, Christoffer Martinussen, Kaare V. Grunddal, C. Christiansen, Jens J. Holst, Richard G. Kay, Modvig, Ida M. [0000-0002-6824-2802], Reimann, Frank [0000-0001-9399-6377], Holst, Jens J. [0000-0001-6853-3805], Apollo - University of Cambridge Repository, Department of Biomedical Sciences [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge [UK] (CAM), Modvig, Ida M [0000-0002-6824-2802], and Holst, Jens J [0000-0001-6853-3805]
Subjects: 0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medicine (miscellaneous), Secretin, fluids and secretions, 0302 clinical medicine, Intestine, Small, Gastrointestinal hormones, 0303 health sciences, education.field_of_study, Nutrition and Dietetics, Chemistry, Glucagon secretion, article, Endocrine system and metabolic diseases, Type 2 diabetes, 692/163/2743/393, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Postprandial Period, medicine.anatomical_structure, Pancreas, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, Somatostatin secretion, Enteroendocrine Cells, Population, Gastric Bypass, 030209 endocrinology & metabolism, 631/45/776/198, Glucagon, digestive system, 692/163/2743/137/773, 38/91, 14/32, 03 medical and health sciences, Internal medicine, medicine, Animals, Obesity, 631/443/319, Rats, Wistar, education, 82/83, 030304 developmental biology, business.industry, Insulin, 82/58, nutritional and metabolic diseases, digestive system diseases, Small intestine, Rats, 030104 developmental biology, Metabolism, Glucose, Endocrinology, 692/163/2743, business, 82/51
Abstract: ObjectivesGastrointestinal hormones contribute to the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB) on glycemic control. Secretin is secreted from duodenal S cells in response to low luminal pH, but it is unknown whether its secretion is altered after RYGB and if secretin contributes to the postoperative improvement in glycemic control. We hypothesized that secretin secretion increases after RYGB as a result of the diversion of nutrients to more distal parts of the small intestine, and thereby affects islet hormone release.MethodsA specific secretin radioimmunoassay was developed, evaluated biochemically, and used to quantify plasma concentrations of secretin in 13 obese individuals before, 1 week after, and 3 months after RYGB. Distribution of secretin and its receptor was assessed by RNA sequencing, mass-spectrometry and in situ hybridization in human and rat tissues. Isolated, perfused rat intestine and pancreas were used to explore the molecular mechanism underlying glucose-induced secretin secretion and to study direct effects of secretin on glucagon, insulin, and somatostatin secretion. Secretin was administered alone or in combination with GLP-1 to non-sedated rats to evaluate effects on glucose regulation.ResultsPlasma postprandial secretin was more than doubled in humans after RYGB (P P P = 0.2) nor glucagon (P = 0.97) secretion. When administered to rats in vivo, insulin secretion was attenuated and glucagon secretion increased (P = 0.04), while blood glucose peak time was delayed (from 15 to 45 min) and gastric emptying time prolonged (P = 0.004).ConclusionsGlucose-sensing secretin cells located in the distal part of the small intestine may contribute to increased plasma concentrations observed after RYGB. The metabolic role of the distal S cells warrants further studies.
Published: 2020

27. Adverse effects of reduced oxygen tension on the proliferative capacity of rat kidney and insulin-secreting cell lines involve DNA damage and stress responses

Author: Ozanne, Susan [Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ (United Kingdom)]
Published: 2008
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28. Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet

Author: Emma, Erik Elias, Bauke Haisma, Fiona M. Gribble, Erik Elebring, Carel W. le Roux, Neil G. Docherty, Ville Wallenius, Pierre Larraufie, Frank Reimann, Anna Casselbrant, Lars Fändriks, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge [UK] (CAM), Wallenius, Ville [0000-0001-8668-3196], Elias, Erik [0000-0002-1624-3432], Larraufie, Pierre [0000-0001-7718-6200], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Hydroxymethylglutaryl-CoA Synthase, Male, Enteroendocrine cell, Ketone Bodies, medicine.disease_cause, Small Bowel, Jejunum, Mice, 0302 clinical medicine, Glucagon-Like Peptide 1, Ketogenesis, Postoperative Period, Intestinal Mucosa, Cells, Cultured, Phospholipids, 2. Zero hunger, 3-Hydroxybutyric Acid, Gastroenterology, Peptide secretion, Ketones, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Very low calorie diet, medicine.anatomical_structure, Liver, Preoperative Period, diabetes mellitus, Ketone bodies, Emulsions, Female, enterocyte biology, medicine.medical_specialty, Fat Emulsions, Intravenous, food.diet, Enteroendocrine Cells, Primary Cell Culture, Gastric Bypass, 030209 endocrinology & metabolism, Glucagon, 03 medical and health sciences, food, Internal medicine, medicine, Animals, Humans, Caloric Restriction, Gastric bypass surgery, business.industry, nutritional and metabolic diseases, Anastomosis, Roux-en-Y, glucagen-like peptides, Dietary Fats, Soybean Oil, obesity surgery, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, business
Abstract: ObjectiveFood intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised this to be a result of the metabolic changes taking place in the small intestinal mucosa following the anatomical rearrangement after RYGB surgery, and aimed at identifying such mechanisms.DesignJejunal mucosa biopsies from patients undergoing RYGB surgery were retrieved before and after very-low calorie diet, at time of surgery and 6 months postoperatively. Samples were analysed by global protein expression analysis and Western blotting. Biological functionality of these findings was explored in mice and enteroendocrine cells (EECs) primary mouse jejunal cell cultures.ResultsThe most prominent change found after RYGB was decreased jejunal expression of the rate-limiting ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGCS), corroborated by decreased ketone body levels. In mice, prolonged high-fat feeding induced the expression of mHMGCS and functional ketogenesis in jejunum. The effect of ketone bodies on gut peptide secretion in EECs showed a ∼40% inhibition of GLP-1 release compared with baseline.ConclusionIntestinal ketogenesis is induced by high-fat diet and inhibited by RYGB surgery. In cell culture, ketone bodies inhibited GLP-1 release from EECs. Thus, we suggest that this may be a mechanism by which RYGB can remove the inhibitory effect of ketone bodies on EECs, thereby restituting the responsiveness of EECs resulting in increased meal-stimulated levels of GLP-1 after surgery.
Published: 2019

29. Single cell transcriptomic profiling of large intestinal enteroendocrine cells in mice – Identification of selective stimuli for insulin-like peptide-5 and glucagon-like peptide-1 co-expressing cells

Author: Fiona M. Gribble, Jo E. Lewis, Richard G. Kay, Pierre Larraufie, Joyce Li, Frank Reimann, Brian Y.H. Lam, Giles Sh Yeo, Deborah A. Goldspink, Andrew B. Leiter, Lawrence J. Billing, Wellcome Trust-MRC Institute of Metabolic Science, Reimann, Frank [0000-0001-9399-6377], Larraufie, Pierre [0000-0001-7718-6200], Yeo, Giles [0000-0001-8823-3615], Kay, Richard [0000-0002-3827-8687], Gribble, Fiona [0000-0002-4232-2898], and Apollo - University of Cambridge Repository
Subjects: Male, 0301 basic medicine, lcsh:Internal medicine, Mice, Transgenic, 030209 endocrinology & metabolism, Enteroendocrine cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Tryptophan Hydroxylase, Receptor, Angiotensin, Type 1, Secretin, Mice, 03 medical and health sciences, 0302 clinical medicine, Single-cell analysis, Glucagon-Like Peptide 1, Animals, Insulin, Peptide YY, Intestine, Large, Receptor, lcsh:RC31-1245, Insulin-like peptide-5 (Insl5), Molecular Biology, Cholecystokinin, Enteroendocrine cells, Chemistry, Serotonin (5-HT), Single cell RNA-sequencing, digestive, oral, and skin physiology, Proteins, Cell Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Angiotensin II, 3. Good health, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Enterochromaffin cell, Female, Original Article, Single-Cell Analysis, Transcriptome, Corrigendum, hormones, hormone substitutes, and hormone antagonists, Glucagon-like peptide-1 (GLP-1)
Abstract: Objective Enteroendocrine cells (EECs) of the large intestine, found scattered in the epithelial layer, are known to express different hormones, with at least partial co-expression of different hormones in the same cell. Here we aimed to categorize colonic EECs and to identify possible targets for selective recruitment of hormones. Methods Single cell RNA-sequencing of sorted enteroendocrine cells, using NeuroD1-Cre x Rosa26-EYFP mice, was used to cluster EECs from the colon and rectum according to their transcriptome. G-protein coupled receptors differentially expressed across clusters were identified, and, as a proof of principle, agonists of Agtr1a and Avpr1b were tested as candidate EEC secretagogues in vitro and in vivo. Results EECs from the large intestine separated into 7 clear clusters, 4 expressing higher levels of Tph1 (enzyme required for serotonin (5-HT) synthesis; enterochromaffin cells), 2 enriched for Gcg (encoding glucagon-like peptide-1, GLP-1, L-cells), and the 7th expressing somatostatin (D-cells). Restricted analysis of L-cells identified 4 L-cell sub-clusters, exhibiting differential expression of Gcg, Pyy (Peptide YY), Nts (neurotensin), Insl5 (insulin-like peptide 5), Cck (cholecystokinin), and Sct (secretin). Expression profiles of L- and enterochromaffin cells revealed the clustering to represent gradients along the crypt-surface (cell maturation) and proximal-distal gut axes. Distal colonic/rectal L-cells differentially expressed Agtr1a and the ligand angiotensin II was shown to selectively increase GLP-1 and PYY release in vitro and GLP-1 in vivo. Conclusion EECs in the large intestine exhibit differential expression gradients along the crypt-surface and proximal-distal axes. Distal L-cells can be differentially stimulated by targeting receptors such as Agtr1a., Graphical abstract Image 1, Highlights • Large intestinal enteroendocrine cells group into subclusters by single cell RNAseq. • Enteroendocrine-cell subclusters differ along crypt-surface and longitudinal axes. • L-cells differ longitudinally by production of NTS (proximal colon) or INSL5 (rectum). • INSL5-positive cells express distinct GPCRs enabling cluster-specific stimulation. • Targeted stimulation of INSL5-producing L-cells elevates plasma GLP-1 and PYY in vivo.
Published: 2019

30. Abcc5 knockout mice have lower fat mass and increased levels of circulating GLP‐1

Author: Heidi de Wet, Luke Cotter, James Cantley, Fiona M. Gribble, Pierre Larraufie, Frank Reimann, Malgorzata Cyranka, Pamela V. Lear, Affan Saibudeen, Elizabeth Bentley, Michelle Stewart, Eleanor J McKay, Anna Veprik, James S. O. McCullagh, Swathi Lingam, Roger D. Cox, Elisabete Pires, Nisha Hare, Amber Thijsse, Nienke van Loon, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge [UK] (CAM), de Wet, Heidi [0000-0002-9871-6909], and Apollo - University of Cambridge Repository
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medicine (miscellaneous), 030209 endocrinology & metabolism, Enteroendocrine cell, Type 2 diabetes, Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Endocrinology, Glucagon-Like Peptide 1, Diabetes mellitus, Internal medicine, medicine, Glucose homeostasis, Animals, Homeostasis, Insulin, 030212 general & internal medicine, 2. Zero hunger, Mice, Knockout, Glucose tolerance test, Nutrition and Dietetics, medicine.diagnostic_test, Original Articles, Glucose Tolerance Test, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Obesity, Adipose Tissue, Diabetes Mellitus, Type 2, Knockout mouse, Original Article, Obesity Biology and Integrated Physiology, Insulin Resistance, Multidrug Resistance-Associated Proteins, Genome-Wide Association Study
Abstract: Objective A previous genome‐wide association study linked overexpression of an ATP‐binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse. Methods A global Abcc5‐/‐ mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon‐like peptide 1 (GLP‐1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme‐linked immunosorbent assay. Results Abcc5‐/‐ mice had decreased fat mass and increased plasma levels of GLP‐1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP‐1 release. Conclusions ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP‐1 secretion from enteroendocrine cells.
Published: 2019

31. Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients

Author: Pierre Larraufie, Frank Reimann, Niels Jessen, Fiona M. Gribble, Niels Møller, Esben Thyssen Vestergaard, Rune E. Kuhre, Jens Otto Lunde Jørgensen, Jens J. Holst, Astrid Hjelholt, and Wellcome Trust-MRC Institute of Metabolic Science
Subjects: 0301 basic medicine, Blood Glucose, Male, Acipimox, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, NICOTINIC-ACID, ENTEROENDOCRINE CELLS, Pilot Projects, Type 2 diabetes, Fatty Acids, Nonesterified, Biochemistry, 0302 clinical medicine, Endocrinology, Glucagon-Like Peptide 1, Medicine, Intestinal Mucosa, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Hypolipidemic Agents, PLASMA-GLUCOSE, Glucose tolerance test, Cross-Over Studies, medicine.diagnostic_test, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, INSULIN, 3. Good health, ADIPOSE-TISSUE, Pyrazines, GROWTH-HORMONE, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, medicine.medical_specialty, Enteroendocrine Cells, Lipolysis, Primary Cell Culture, 030209 endocrinology & metabolism, Context (language use), METABOLISM, Article, Hypopituitarism, 03 medical and health sciences, Insulin resistance, Internal medicine, Animals, Humans, business.industry, Insulin, Biochemistry (medical), FREE FATTY-ACID, Glucose Tolerance Test, Overweight, DEGRADATION, medicine.disease, Crossover study, Rats, 030104 developmental biology, PYY SECRETION, Insulin Resistance, business
Abstract: Context Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a) receptor. Objective To investigate whether lowering of serum FFA level with acipimox affects GLP-1 secretion. Design Two randomized crossover studies were performed in human subjects. Rat intestine was perfused intra-arterially and intraluminally, and l-cells were incubated with acipimox. Participants The participants were healthy overweight subjects and hypopituitary adult patients. Interventions The overweight participants received acipimox 250 mg 60 minutes before an oral glucose test. The hypopituitary patients received acipimox 250 mg 12, 9, and 2 hours before and during the metabolic study day, when they were studied in the basal state and during a hyperinsulinemic euglycemic clamp. Results Acipimox suppressed FFA but did not affect insulin in the clinical trials. In overweight subjects, the GLP-1 increase after the oral glucose tolerance test (area under the curve) was more than doubled [4119 ± 607 pmol/L × min (Acipimox) vs 1973 ± 375 pmol/L × min (control), P = 0.004]. In hypopituitary patients, acipimox improved insulin sensitivity (4.7 ± 0.8 mg glucose/kg/min (Acipimox) vs 3.1 ± 0.5 mg glucose/kg/min (control), P = 0.005], and GLP-1 concentrations increased ~40%. An inverse correlation between FFA and GLP-1 concentrations existed in both trials. In rat intestine, acipimox did not affect GLP-1 secretion, and l-cells did not consistently express the putative receptor for acipimox. Conclusions Acipimox treatment increases systemic GLP-1 levels in both obese subjects and hypopituitary patients. Our in vitro data indicate that the underlying mechanisms are indirect.
Published: 2019

32. Associations of circulating very-long-chain saturated fatty acids and incident type 2 diabetes:a pooled analysis of prospective cohort studies

Author: Matti Marklund, Sari Voutilainen, Claudine Berr, Nicholas J. Wareham, Dariush Mozaffarian, Albert Koulman, Cécilia Samieri, Ingeborg A. Brouwer, Jenna Veenstra, Amanda M. Fretts, Luc Djoussé, David S. Siscovick, V. Gudnason, Lynne E. Wagenknecht, Lyn M. Steffen, Maria Lankinen, Michael Y. Tsai, Nathan L. Tintle, Nona Sotoodehnia, Jyrki K. Virtanen, Fumiaki Imamura, Barbara McKnight, Catherine Helmer, Kuo-Liong Chien, Kerry L. M. Wong, Jason H Y Wu, Rozenn N. Lemaitre, Bill Harris, Chaoyu Yu, Renata Micha, Matti Uusitupa, Tamara B. Harris, Kalina Rajaobelina, Nita G. Forouhi, Alexis C. Wood, Waqas Qureshi, Rachel A. Murphy, Markku Laakso, Brian T. Steffen, Anya Kalsbeek, Cardiovascular Health Research Unit [Seattle, WA, USA] (Department of Medicine), University of Washington [Seattle], MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Departments of Epidemiology and Nutrition, Harvard School of Public Health, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), MRC epidemiology Unit, Addenbrooke's Hospital, Department of Medicine, Kuopio University Hospital, NIHR Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Icelandic Heart Association, Kopavogur, Iceland., School of Public Health and Clinical Nutrition, University of Eastern Finland, Laboratory Medicine and Pathology in Minnesota [Rochester], Mayo Clinic, Institute of Public Health and Clinical Nutrition, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Berr, Claudine, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition and Health, APH - Health Behaviors & Chronic Diseases, and APH - Mental Health
Subjects: Adult, Male, medicine.medical_specialty, Percentile, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Lignoceric acid, 030209 endocrinology & metabolism, Type 2 diabetes, Lower risk, Logistic regression, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Eicosanoic Acids, Internal medicine, Diabetes mellitus, Medicine, Humans, saturated fatty acids, Prospective Studies, Prospective cohort study, 030304 developmental biology, Aged, 2. Zero hunger, Aged, 80 and over, 0303 health sciences, Nutrition and Dietetics, Fatty Acids and Outcomes Research Consortium, diabetes, business.industry, Fatty Acids, Middle Aged, medicine.disease, 3. Good health, very-long-chain saturated fatty acids, [SDV] Life Sciences [q-bio], meta-analysis, Original Research Communications, chemistry, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Meta-analysis, Cohorts for Heart and Aging Research in Genomic Epidemiology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; BACKGROUND:Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed.OBJECTIVE:We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies.METHODS:Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants.RESULTS:There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides.CONCLUSIONS:Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.
Published: 2019

33. Comparison of Human and Murine Enteroendocrine Cells by Transcriptomic and Peptidomic Profiling

Author: Fiona M. Gribble, Geoffrey P. Roberts, Marcella Ma, Brian Y.H. Lam, Raphael Scharfmann, Davide Chiarugi, Pierre Larraufie, Richard H. Hardwick, Richard G. Kay, Frank Reimann, Leslie L Glass, Paul Richards, Joyce Li, Giles S.H. Yeo, Emily L. Miedzybrodzka, Sam G Galvin, Andrew B. Leiter, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge [UK] (CAM), Roberts, Geoffrey P [0000-0001-9554-8404], Scharfmann, Raphaël [0000-0001-7619-337X], Gribble, Fiona M [0000-0002-4232-2898], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Enteroendocrine Cells, Peptide, 030209 endocrinology & metabolism, Enteroendocrine cell, Peptide hormone, Biology, Receptors, G-Protein-Coupled, Transcriptome, 03 medical and health sciences, Mice, 0302 clinical medicine, Glucagon-Like Peptide 1, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal Medicine, Animals, Humans, Secretion, Receptor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Drug discovery, RNA, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cell biology, stomatognathic diseases, 030104 developmental biology, chemistry, Diabetes Mellitus, Type 2, Peptide YY, Hormone
Abstract: Enteroendocrine cells (EECs) produce hormones such as glucagon-like peptide 1 and peptide YY that regulate food absorption, insulin secretion, and appetite. Based on the success of glucagon-like peptide 1–based therapies for type 2 diabetes and obesity, EECs are themselves the focus of drug discovery programs to enhance gut hormone secretion. The aim of this study was to identify the transcriptome and peptidome of human EECs and to provide a cross-species comparison between humans and mice. By RNA sequencing of human EECs purified by flow cytometry after cell fixation and staining, we present a first transcriptomic analysis of human EEC populations and demonstrate a strong correlation with murine counterparts. RNA sequencing was deep enough to enable identification of low-abundance transcripts such as G-protein–coupled receptors and ion channels, revealing expression in human EECs of G-protein–coupled receptors previously found to play roles in postprandial nutrient detection. With liquid chromatography–tandem mass spectrometry, we profiled the gradients of peptide hormones along the human and mouse gut, including their sequences and posttranslational modifications. The transcriptomic and peptidomic profiles of human and mouse EECs and cross-species comparison will be valuable tools for drug discovery programs and for understanding human metabolism and the endocrine impacts of bariatric surgery.
Published: 2019
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34. PYY plays a key role in the resolution of diabetes following bariatric surgery in humans

Author: Guida, C, Stephen, SD, Watson, M, Dempster, N, Larraufie, P, Marjot, T, Cargill, T, Rickers, L, Pavlides, M, Tomlinson, J, Cobbold, JFL, Zhao, C-M, Chen, D, Gribble, F, Reimann, F, Gillies, R, Sgromo, B, Rorsman, OP, Ryan, JD, Ramracheya, RD, Wellcome Trust-MRC Institute of Metabolic Science, Larraufie, Pierre [0000-0001-7718-6200], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], and Apollo - University of Cambridge Repository
Subjects: Bariatric surgery, Male, PYY, Enteroendocrine Cells, Interleukins, Diabetes, digestive, oral, and skin physiology, Gene Expression, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Gut hormones, Pancreatic hormone secretion, Rats, Islets of Langerhans, Mice, Diabetes Mellitus, Type 2, Glucagon-Like Peptide 1, IL-22, Animals, Humans, Female, Peptide YY, Biomarkers
Abstract: Background Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic isletsecretory function and glucose metabolism remains under-studied. Methods Changes in PYY concentrations were examined in obese patients after bariatric surgery and compared to healthy controls. Human pancreatic islet function was tested upon treatment with sera from patients before and after the surgery, in presence or absence of PYY. Alterations in intra-islet PYY release and insulin secretion were analysed after stimulation with short chain fatty acids (SCFAs), bile acids and the cytokine IL-22. Findings We demonstrate that PYY is a key effector of the early recovery of impaired glucose-mediated insulin and glucagon secretion in bariatric surgery. We establish that the short chain fatty acid propionate and bile acids, which are elevated after surgery, can trigger PYY release not only from enteroendocrine cells but also from human pancreatic islets. In addition, we identify IL-22 as a new factor which is modulated by bariatric surgery in humans and which directly regulates PYY expression and release. Interpretation This study shows that some major metabolic benefits of bariatric surgery can be emulated ex vivo. Our findings are expected to have a direct impact on the development of new non-surgical therapy for T2D correction. (C) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Published: 2019

35. GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

Author: Patel, S., Alvarez-Guaita, A., Melvin, A., Rimmington, D., Dattilo, A., Miedzybrodzka, E. L., Cimino, I., Maurin, Anne-Catherine, Roberts, G. P., Meek, C. L., Virtue, S., Sparks, L. M., Parsons, S. A., Redman, L. M., Bray, G. A., Liou, A. P., Woods, R. M., Parry, S. A., Jeppesen, P. B., Kolnes, A. J., Harding, H. P., Ron, D., Vidal-Puig, A., Reimann, F., Gribble, F. M., Hulston, C. J., Farooqi, I. S., Fafournoux, Pierre, Smith, S. R., Jensen, J., Breen, D., Wu, Z., Zhang, B. B., Coll, A. P., Savage, D. B., O'Rahilly, S., Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Wellcome Trust-MRC Institute of Metabolic Science (IMS), University of Cambridge, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Pennington Biomedical Research Center, Internal Medicine Research Unit (IMRU - BUENOS AIRES), Hospital Italiano - BUENOS AIRES (Hop It - BUENOS AIRES), School of Sport, Exercise and Health Sciences, Loughborough University, Department of Clinical Medicine, Örebro University, Aarhus University, Department of Endocrinology, John Vane Science Center-Barts and the London Medical School, Metabolic Research Laboratories, Department of Physical Performance, Norwegian School of Sport Sciences, Aarhus University [Aarhus], Norwegian School of Sport Sciences = Norges idrettshøgskole [Oslo] (NIH), Patel, Satish [0000-0002-5345-8942], Cimino, Irene [0000-0003-1397-5408], Meek, Claire [0000-0002-4176-8329], Harding, Heather [0000-0002-7359-7974], Ron, David [0000-0002-3014-5636], Vidal-Puig, Antonio [0000-0003-4220-9577], Reimann, Frank [0000-0001-9399-6377], Gribble, Fiona [0000-0002-4232-2898], Farooqi, Ismaa [0000-0001-7609-3504], Coll, Anthony [0000-0003-2594-7463], Savage, David [0000-0002-7857-7032], O'Rahilly, Stephen [0000-0003-2199-4449], and Apollo - University of Cambridge Repository
Subjects: Adult, Gdf15, Growth Differentiation Factor 15, Endocrinology, Diabetes and Metabolism, MEDLINE, overnutrion, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Bioinformatics, Diet, High-Fat, Article, Cell Line, Mice, Young Adult, Endocrinology, Text mining, Gfral, Stress (linguistics), Medicine, Animals, Humans, conditioned taste aversion, health care economics and organizations, ComputingMilieux_MISCELLANEOUS, GFRAL, business.industry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, integrated stress response, Middle Aged, Mice, Inbred C57BL, GDF15, business, Energy Intake, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Summary GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress., Graphical Abstract, Highlights • Dietary changes influencing adipose/gut-derived hormones do not alter GDF15 levels • Chronic high-fat or acute lysine-deficient diet exposure increases GDF15 levels • GDF15 administration triggers conditioned taste aversion in mice • GDF15 is a stress-induced hormone that may mediate an aversive dietary response, Patel et al. show that whereas short-term overfeeding or fasting does not change GDF15 levels substantially, prolonged high-fat feeding and lysine-deficient diets activate the integrated stress response and increase GDF15 levels. GDF15 administration triggers conditioned taste aversion in mice, suggesting that GDF15 might induce an aversive response to nutritional stress.
Published: 2019

36. Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum

Author: Parker, Victoria, Keppler-Noreuil, Kim, Faivre, Laurence, Luu, Maxime, Oden, Neal, De Silva, Leena, Sapp, Julie, Andrews, Katrina, Bardou, Marc, Chen, Kong, Darling, Thomas, Gautier, Elodie, Goldspiel, Barry, Hadj-Rabia, Smail, Harris, Julie, Kounidas, Georgios, Kumar, Parag, Lindhurst, Marjorie, Loffroy, Romaric, Martin, Ludovic, Phan, Alice, Rother, Kristina, Widemann, Brigitte, Wolters, Pamela, Coubes, Christine, Pinson, Lucile, Willems, Marjolaine, Vincent-Delorme, Catherine, PROMISE working group,, Vabres, Pierre, Semple, Robert, Biesecker, Leslie, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge [UK] (CAM), National Human Genome Research Institute (NHGRI), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, FHU TRANSLAD (CHU de Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), The EMMES Corporation, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Uniformed Services University of the Health Sciences (USUHS), Pharmacy Department (NIH Clinical Center National, Institutes of Health), National Institutes of Health [Bethesda] (NIH), Centre de référence national des Maladies Génétiques à Expression Cutanée (MAGEC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Département de dermatologie, CHU Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Génétique Médicale [Lille], Institut de génétique médicale-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Queen's Medical Researche Institute, University of Edinburgh, CHU Necker - Enfants Malades [AP-HP]-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier]
Subjects: Adult, Male, Adolescent, Class I Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases, PIK3CA, Middle Aged, Article, Phosphatidylinositol 3-Kinases, Phenotype, sirolimus, mosaicism, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, Mutation, Humans, Abnormalities, Multiple, Female, Child, overgrowth, Growth Disorders, Aged
Abstract: PurposePIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth.MethodsThirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy.ResultsThirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of –7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently.ConclusionThis study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk–benefit evaluations for sirolimus treatment in PROS.
Published: 2019

37. Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis

Author: Kirwan, Peter, Kay, Richard G., Brouwers, Bas, Herranz-Pérez, Vicente, Jura, Magdalena, Larraufie, Pierre, Jerber, Julie, Pembroke, Jason, Bartels, Theresa, White, Anne, Gribble, Fiona M., Reimann, Frank, Farooqi, I. Sadaf, O'Rahilly, Stephen, Merkle, Florian T., Wellcome Trust-MRC Institute of Metabolic Science, Kirwan, Peter [0000-0003-1446-7544], Kay, Richard [0000-0002-3827-8687], Larraufie, Pierre [0000-0001-7718-6200], Bartels, Theresa [0000-0003-4100-0608], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], Farooqi, Ismaa [0000-0001-7609-3504], O'Rahilly, Stephen [0000-0003-2199-4449], Merkle, Florian [0000-0002-8513-2998], and Apollo - University of Cambridge Repository
Subjects: Male, Pluripotent Stem Cells, Leptin, lcsh:Internal medicine, endocrine system, hPSC, human pluripotent stem cells, Pro-Opiomelanocortin, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hypothalamus, Mass Spectrometry, Tandem Mass Spectrometry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], beta-MSH, Homeostasis, Humans, Human pluripotent stem cell, Obesity, lcsh:RC31-1245, MSH, Neurons, integumentary system, Receptors, Melanocortin, LC-MS/MS, liquid chromatography tandem mass spectrometry, Neuropeptides, digestive, oral, and skin physiology, POMC, PVH, the paraventricular nucleus of the hypothalamus, CTX, cerebral cortex, Melanocortins, Neuropeptide, alpha-MSH, Original Article, Female, hormones, hormone substitutes, and hormone antagonists, Chromatography, Liquid
Abstract: Objective The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated. Methods We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from human pluripotent stem cells (hPSCs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the sequence and quantify the production of hypothalamic neuropeptides, including those derived from POMC. Results In both in vitro and in vivo hypothalamic cells, LC-MS/MS revealed the sequence of hundreds of neuropeptides as a resource for the field. Although the existence of β-melanocyte stimulating hormone (MSH) is controversial, we found that both this peptide and desacetyl α-MSH (d-α-MSH) were produced in considerable excess of acetylated α-MSH. In hPSC-derived hypothalamic neurons, these POMC derivatives were appropriately trafficked, secreted, and their production was significantly (P, Highlights • Characterisation of the human hypothalamic peptidome in vitro and in vivo. • hPSC-derived POMC neurons correctly process POMC into peptides important for regulating feeding and energy balance, including β-MSH. • β-MSH and desacetyl α-MSH are produced in excess of acetylated α-MSH in primary and hPSC-derived human hypothalamic cells. • Leptin significantly increases the production of human POMC-derived peptides.
Published: 2018

38. Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort

Author: Roel Vermeulen, J. Ramón Quirós, Torkjel M. Sandanger, Domenico Palli, Carlotta Sacerdote, Gianluca Severi, Eva Ardanaz, Bas Bueno-de-Mesquita, Sara Grioni, Malin Sund, Rudolf Kaaks, Manuela M. Bergmann, Matthias B. Schulze, Federico Canzian, Miguel Rodríguez-Barranco, Luca Morelli, Carlo La Vecchia, Pietro Ferrari, Salvatore Panico, Anna Karakatsani, Theron Johnson, Pilar Amiano, Kay-Tee Khaw, Nicholas J. Wareham, Paula Jakszyn, Sandra Colorado-Yohar, Daniele Campa, Marie-Christine Boutron-Ruault, Julie A. Schmidt, Rosario Tumino, Anne Tjønneland, Verena Katzke, Vittorio Perduca, Manuel Gentiluomo, Antonia Trichopoulou, Elisabete Weiderpass, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Danish Cancer Society, Cancer Epidemiology Centre, Cancer Council Victoria, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Nutrition and Metabolism Section, International Agency for Research on Cancer, Deutsches Krebsforschungszentrum, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Dept of Epidemiology, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), Istituto per lo Studio e la Prevezione Oncologica, Partenaires INRAE, Epidemiology, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Civile - M.P.Arezzo Hospital, CPO Piemonte, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Division of Environmental Epidemiology, Utrecht University [Utrecht]-Institute of Risk Assessment Sciences, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Surgery and Perioperative Sciences, Umea University Hospital, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L´Hospitallet de Llobregat, Department of Pathology, Santa Chiara Hospital, Department of Cancer Epidemiology, One Health Chemisch, dIRAS RA-2, Gentiluomo, Manuel [0000-0002-0366-9653], Katzke, Verena A [0000-0002-6509-6555], Tjønneland, Anne [0000-0003-4385-2097], Perduca, Vittorio [0000-0003-0339-0473], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Weiderpass, Elisabete [0000-0003-2237-0128], Johnson, Theron [0000-0003-4850-282X], Bergmann, Manuela [0000-0001-5064-227X], Karakatsani, Anna [0000-0002-3275-2026], La Vecchia, Carlo [0000-0003-1441-897X], Palli, Domenico [0000-0002-5558-2437], Grioni, Sara [0000-0002-5891-8426], Tumino, Rosario [0000-0003-2666-414X], Ardanaz, Eva [0000-0001-8434-2013], Schmidt, Julie A [0000-0002-7733-8750], Morelli, Luca [0000-0002-7742-9556], Canzian, Federico [0000-0002-4261-4583], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Mitochondrial DNA, Pancreatic ductal adenocarcinoma, DNA Copy Number Variations, Epidemiology, EPIC, Real-Time Polymerase Chain Reaction, DNA, Mitochondrial, Risk Assessment, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Pancreatic cancer, medicine, Biomarkers, Tumor, Leukocytes, Humans, Copy-number variation, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, 2. Zero hunger, business.industry, Incidence, Age Factors, Middle Aged, Protective Factors, medicine.disease, Peripheral blood, 3. Good health, Mitochondria, Europe, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business
Abstract: Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10−5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16–0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07–0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.
Published: 2020

39. Co-storage and release of insulin-like peptide-5, glucagon-like peptide-1 and peptideYY from murine and human colonic enteroendocrine cells

Author: Billing, Lawrence J, Smith, Christopher A, Larraufie, Pierre, Goldspink, Deborah A, Galvin, Sam, Kay, Richard G, Howe, Jonathan D, Walker, Ryan, Pruna, Mihai, Glass, Leslie, Pais, Ramona, Gribble, Fiona M, Reimann, Frank, Wellcome Trust-MRC Institute of Metabolic Science, Larraufie, Pierre [0000-0001-7718-6200], Galvin, Sam [0000-0001-5910-9471], Kay, Richard [0000-0002-3827-8687], Glass, Leslie [0000-0002-3559-4705], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], and Apollo - University of Cambridge Repository
Subjects: lcsh:Internal medicine, Colon, Enteroendocrine Cells, Peptide Hormones, Primary Cell Culture, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, peptideYY (PYY), Mass Spectrometry, Insulin-like peptide-5 (INSL5), Receptors, G-Protein-Coupled, Gastrointestinal Hormones, Mice, Glucagon-Like Peptide 1, 3D-SIM, Animals, Humans, Insulin, Peptide YY, Enteroendocrine, lcsh:RC31-1245, Cells, Cultured, Intestinal Secretions, digestive, oral, and skin physiology, Proteins, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, LC-MS, Human colonic cultures, L-cell, hormones, hormone substitutes, and hormone antagonists, Chromatography, Liquid, Glucagon-like peptide-1 (GLP-1)
Abstract: Objective: Insulin-like peptide-5 (INSL5) is an orexigenic gut hormone found in a subset of colonic and rectal enteroendocrine L-cells together with the anorexigenic hormones glucagon-like peptide-1 (GLP-1) and peptideYY (PYY). Unlike GLP-1 and PYY, INSL5 levels are elevated by calorie restriction, raising questions about how these hormones respond to different stimuli when they arise from the same cell type. The aim of the current study was to identify whether and how INSL5, GLP-1 and PYY are co-secreted or differentially secreted from colonic L-cells. Methods: An inducible reporter mouse (Insl5-rtTA) was created to enable selective characterisation of Insl5-expressing cells. Expression profiling and Ca2+-dynamics were assessed using TET-reporter mice. Secretion of INSL5, PYY, and GLP-1 from murine and human colonic crypt cultures was quantified by tandem mass spectrometry. Vesicular co-localisation of the three hormones was analysed in 3D-SIM images of immunofluorescently-labelled murine colonic primary cultures and tissue sections. Results: INSL5-producing cells expressed a range of G-protein coupled receptors previously identified in GLP-1 expressing L-cells, including Ffar1, Gpbar1, and Agtr1a. Pharmacological or physiological agonists for these receptors triggered Ca2+ transients in INSL5-producing cells and stimulated INSL5 secretion. INSL5 secretory responses strongly correlated with those of PYY and GLP-1 across a range of stimuli. The majority (>80%) of secretory vesicles co-labelled for INSL5, PYY and GLP-1. Conclusions: INSL5 is largely co-stored with PYY and GLP-1 and all three hormones are co-secreted when INSL5-positive cells are stimulated. Opposing hormonal profiles observed in vivo likely reflect differential stimulation of L-cells in the proximal and distal gut. Keywords: Insulin-like peptide-5 (INSL5), Glucagon-like peptide-1 (GLP-1), peptideYY (PYY), Enteroendocrine, L-cell, LC-MS, Human colonic cultures, 3D-SIM
Published: 2018

40. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Author: Yiallouros, Panayiotis K., Escobedo-de la Peña, Jorge, Zhou, Bin, Bentham, James, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M., Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charles, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, James, Bilano, Ver, Stevens, Gretchen A., Cowan, Melanie J., Riley, Leanne M., Chen, Zhengming, Hambleton, Ian R., Jackson, Rod T., Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K., Sorić, Maroje, Starc, Gregor, Sundström, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gómez, Leandra, Abdeen, Ziad A., Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M., Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N., Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A., Ängquist, Lars H., Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assunção, Maria Cecília F., Avdicová, Mária, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V., Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R., Barbagallo, Carlo M., Barceló, Alberto, Barkat, Amina, Barros, Aluisio J. D., Barros, Mauro V., Bata, Iqbal, Batieha, Anwar M., Batyrbek, Assembekov, Baur, Louise A., Beaglehole, Robert, Romdhane, Habiba Ben, Benet, Mikhail, Benson, Lowell S., Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K., Bi, Yufang, Bikbov, Mukharram, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Björkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G., Boissonnet, Carlos P., Bongard, Vanina, Borchini, Rossana, Bovet, Pascal, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M., Bruno, Graziella, Bueno-de-Mesquita, H. B(as), Bugge, Anna, Burns, Con, Bursztyn, Michael, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Günay, Cândido, Ana Paula C., Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Christofaro, Diego G., Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, Els, Concin, Hans, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crujeiras, Ana B., Cruz, Juan J., D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M., Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abbas, Delisle, Hélène, Deschamps, Valérie, Dhana, Klodian, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T., Do, Ha T. P., Donfrancesco, Chiara, Donoso, Silvana P., Döring, Angela, Dorobantu, Maria, Doua, Kouamelan, Drygas, Wojciech, Dulskiene, Virginija, Džakula, Aleksandar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Elosua, Roberto, Erasmus, Rajiv T., Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G., Evans, Alun, Faeh, David, Fall, Caroline H., Farzadfar, Farshad, Felix-Redondo, Francisco J., Ferguson, Trevor S., Fernandes, Romulo A., Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D., Fischer, Krista, Föger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M., Francis, Damian K., do Carmo Franco, Maria, Franco, Oscar H., Frontera, Guillermo, Fuchs, Flavio D., Fuchs, Sandra C., Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Galvano, Fabio, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P., Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M., Ghasemian, Anoosheh, Ghimire, Anup, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K., Giovannelli, Jonathan, Goldsmith, Rebecca A., Gonçalves, Helen, Gonzalez-Gross, Marcela, González-Rivas, Juan P., Gorbea, Mariano Bonet, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G., Gregor, Ronald D., Grodzicki, Tomasz, Grøntved, Anders, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F., Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L., Gulliford, Martin C., Gunnlaugsdottir, Johanna, Gunter, Marc, Gupta, Prakash C., Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Halkjær, Jytte, Hardy, Rebecca, Hari Kumar, Rachakulla, Hata, Jun, Hayes, Alison J., He, Jiang, He, Yuna, Elisabeth, Marleen, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Hofman, Albert, Dinc, Gonul Horasan, Horimoto, Andrea R. V. R., Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Than Htike, Maung Maung, Hu, Yonghua, Huerta, José María, Huisman, Martijn, Husseini, Abdullatif S., Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G., Ibrahim, Mohsen M., Wong, Norazizah Ibrahim, Ikeda, Nayu, Ikram, M. Arfan, Irazola, Vilma E., Islam, Muhammad, al-Safi Ismail, Aziz, Ivkovic, Vanja, Iwasaki, Masanori, Jacobs, Jeremy M., Jaddou, Hashem, Jafar, Tazeen, Jamrozik, Konrad, Janszky, Imre, Jasienska, Grazyna, Jelaković, Ana, Jelaković, Bojan, Jennings, Garry, Jeong, Seung-lyeal, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J., Jonas, Jost B., Jørgensen, Torben, Joshi, Pradeep, Jóźwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Jureša, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O., Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Karki, Khem B., Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C. G., Kengne, Andre P., Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khateeb, Mohammad, Khaw, Kay-Tee, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S., Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M., Kulaga, Zbigniew, Krishna Kumar, R., Kurjata, Pawel, Kusuma, Yadlapalli S., Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E., Le Nguyen Bao, Khanh, Le, Tuyen D., Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimäki, Terho, León-Muñoz, Luz M., Levitt, Naomi S., Li, Yanping, Lilly, Christa L., Lim, Wei-Yen, Lima-Costa, M. Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lars, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lorbeer, Roberto, Lotufo, Paulo A., Lozano, José Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L. L., Machi, Suka, Maggi, Stefania, Magliano, Dianna J., Magriplis, Emmanuella, Majer, Marjeta, Makdisse, Marcia, Malhotra, Rahul, Mallikharjuna Rao, Kodavanti, Malyutina, Sofia, Manios, Yannis, Mann, Jim I., Manzato, Enzo, Margozzini, Paula, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mathiesen, Ellisiv B., Matijasevich, Alicia, Matsha, Tandi E., Mbanya, Jean Claude N., Mc Donald Posso, Anselmo J., McFarlane, Shelly R., McGarvey, Stephen T., McLachlan, Stela, McLean, Rachael M., McLean, Scott B., McNulty, Breige A., Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B., Menon, Geetha R., Meshram, Indrapal I., Metspalu, Andres, Meyer, Haakon E., Mi, Jie, Mikkel, Kairit, Miller, Jody C., Minderico, Cláudia S., Francisco, Juan, Miranda, J. Jaime, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Modesti, Pietro A., Mohamed, Mostafa K., Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Mohd Yusoff, Muhammad Fadhli, Møllehave, Line T., Møller, Niels C., Molnár, Dénes, Momenan, Amirabbas, Mondo, Charles K., Monyeki, Kotsedi Daniel K., Moon, Jin Soo, Moreira, Leila B., Morejon, Alain, Moreno, Luis A., Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Esmaeel Motlagh, Mohammad, Motta, Jorge, Msyamboza, Kelias P., Mu, Thet Thet, Muiesan, Maria L., Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M., Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K., Nangia, Vinay B., Narake, Sameer, Nauck, Matthias, Navarrete-Muñoz, Eva Maria, Ndiaye, Ndeye Coumba, Neal, William A., Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T., Nguyen, Nguyen D., Nguyen, Quang Ngoc, Nguyen, Quang V., Nieto-Martínez, Ramfis E., Niiranen, Teemu J., Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A., Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A., Oliveira, Isabel O., Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M., Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M., Ostovar, Afshin, Otero, Johanna A., Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrios, Park, Soon-Woo, Parnell, Winsome R., Parsaeian, Mahboubeh, Patel, Nikhil D., Pecin, Ivan, Pednekar, Mangesh S., Peer, Nasheeta, Peeters, Petra H., Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C., Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Pham, Son Thai, Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Portegies, Marileen L. P., Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F., Puder, Jardena J., Puiu, Maria, Punab, Margus, Qasrawi, Radwan F., Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricardas, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A., Redon, Josep, Reganit, Paul Ferdinand M., Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Rinke de Wit, Tobias F., Ritti-Dias, Raphael M., Robinson, Sian M., Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A., Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G. R., Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S., Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T., Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A., Santos, Ina S., Nunes dos Santos, Renata, Santos, Rute, Saramies, Jouko L., Sardinha, Luis B., Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savvas, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O., Schöttker, Ben, Schultsz, Constance, Schutte, Aletta E., Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O., Sepanlou, Sadaf G., Sharma, Sanjib K., Shaw, Jonathan E., Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M., Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A., Sjöström, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C., Snijder, Marieke B., So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild I. A., Soric, Maroje, Jérome, Charles Sossa, Soumare, Aicha, Staessen, Jan A., Stathopoulou, Maria G., Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D., Stergiou, George S., Stessman, Jochanan, Stieber, Jutta, Stöckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G., Shyong Tai, E., Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B., Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H., Tjonneland, Anne, Tolonen, Hanna K., Tolstrup, Janne S., Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Torrent, Maties, Traissac, Pierre, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh T. H., Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K., Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L., Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E., Ulmer, Hanno, Uusitalo, Hannu M. T., Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T., Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M., van Valkengoed, Irene G. M., Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Monique Verschuren, W. M., Verstraeten, Roosmarijn, Victora, Cesar G., Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K., Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N., Wagner, Aline, Walton, Janette, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley, Rildo S., Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S. 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Utrecht, Hanoi Univ Publ Hlth, Amsterdam Publ Hlth Res Inst, Consejeria Sanidad Junta Castilla & Leon, Universidade Federal de Minas Gerais (UFMG), Finnish Inst Occupat Hlth, Univ Miguel Hernandez, North Karelian Ctr Publ Hlth, Univ Witwatersrand, Univ Strasbourg, Inst Med Res, Xinjiang Med Univ, St Georges Univ London, Med Univ Vienna, Univ Indonesia, Minist Agr, Fudan Univ, Univ Cyprus, Univ Teknol MARA, Inner Mongolia Med Univ, Zhou, B., Bentham, J., Di Cesare, M., Bixby, H., Danaei, G., Hajifathalian, K., Taddei, C., Carrillo-Larco, R.M., Djalalinia, S., Khatibzadeh, S., Lugero, C., Peykari, N., Zhang, W.Z., Bennett, J., Bilano, V., Stevens, G.A., Cowan, M.J., Riley, L.M., Chen, Z., Hambleton, I.R., Jackson, R.T., Kengne, A.P., Khang, Y.H., Laxmaiah, A., Liu, J., Malekzadeh, R., Neuhauser, H.K., Sorić, M., Starc, G., Sundström, J., Woodward, M., Ezzati, M., Abarca-Gómez, L., Abdeen, Z.A., Abu-Rmeileh, N.M., Acosta-Cazares, B., Adams, R.J., Aekplakorn, W., Afsana, K., Aguilar-Salinas, C.A., Agyemang, C., Ahmad, N.A., Ahmadvand, A., Ahrens, W., Ajlouni, K., Akhtaeva, N., Al-Raddadi, R., Ali, M.M., Ali, O., Alkerwi, A., Aly, E., Amarapurkar, D.N., Amouyel, P., Amuzu, A., Andersen, L.B., Anderssen, S.A., Ängquist, L.H., Anjana, R.M., Ansong, D., Aounallah-Skhiri, H., Araújo, J., Ariansen, I., Aris, T., Arlappa, N., Arveiler, D., Aryal, K.K., Aspelund, T., Assah, F.K., Assunção, MCF, Avdicová, M., Azevedo, A., Azizi, F., Babu, B.V., Bahijri, S., Balakrishna, N., Bamoshmoosh, M., Banach, M., Bandosz, P., Banegas, J.R., Barbagallo, C.M., Barceló, A., Barkat, A., Barros, AJD, Barros, M.V., Bata, I., Batieha, A.M., Batyrbek, A., Baur, L.A., Beaglehole, R., Romdhane, H.B., Benet, M., Benson, L.S., Bernabe-Ortiz, A., Bernotiene, G., Bettiol, H., Bhagyalaxmi, A., Bharadwaj, S., Bhargava, S.K., Bi, Y., Bikbov, M., Bista, B., Bjerregaard, P., Bjertness, E., Bjertness, M.B., Björkelund, C., Blokstra, A., Bo, S., Bobak, M., Boeing, H., Boggia, J.G., Boissonnet, C.P., Bongard, V., Borchini, R., Bovet, P., Braeckman, L., Brajkovich, I., Branca, F., Breckenkamp, J., Brenner, H., Brewster, L.M., Bruno, G., Bueno-de-Mesquita, HBA, Bugge, A., Burns, C., Bursztyn, M., de León, A.C., Cacciottolo, J., Cai, H., Cameron, C., Can, G., Cândido, APC, Capuano, V., Cardoso, V.C., Carlsson, A.C., Carvalho, M.J., Casanueva, F.F., Casas, J.P., Caserta, C.A., Chamukuttan, S., Chan, A.W., Chan, Q., Chaturvedi, H.K., Chaturvedi, N., Chen, C.J., Chen, F., Chen, H., Chen, S., Cheng, C.Y., Dekkaki, I.C., Chetrit, A., Chiolero, A., Chiou, S.T., Chirita-Emandi, A., Chirlaque, M.D., Cho, B., Cho, Y., Christofaro, D.G., Chudek, J., Cifkova, R., Cinteza, E., Claessens, F., Clays, E., Concin, H., Cooper, C., Cooper, R., Coppinger, T.C., Costanzo, S., Cottel, D., Cowell, C., Craig, C.L., Crujeiras, A.B., Cruz, J.J., D'Arrigo, G., d'Orsi, E., Dallongeville, J., Damasceno, A., Dankner, R., Dantoft, T.M., Dauchet, L., Davletov, K., De Backer, G., De Bacquer, D., de Gaetano, G., De Henauw, S., de Oliveira, P.D., De Smedt, D., Deepa, M., Dehghan, A., Delisle, H., Deschamps, V., Dhana, K., Di Castelnuovo, A.F., Dias-da-Costa, J.S., Diaz, A., Dickerson, T.T., Do, HTP, Donfrancesco, C., Donoso, S.P., Döring, A., Dorobantu, M., Doua, K., Drygas, W., Dulskiene, V., Džakula, A., Dzerve, V., Dziankowska-Zaborszczyk, E., Eggertsen, R., Ekelund, U., El Ati, J., Elliott, P., Elosua, R., Erasmus, R.T., Erem, C., Eriksen, L., Eriksson, J.G., Escobedo-de la Peña, J., Evans, A., Faeh, D., Fall, C.H., Farzadfar, F., Felix-Redondo, F.J., Ferguson, T.S., Fernandes, R.A., Fernández-Bergés, D., Ferrante, D., Ferrari, M., Ferreccio, C., Ferrieres, J., Finn, J.D., Fischer, K., Föger, B., Foo, L.H., Forslund, A.S., Forsner, M., Fouad, H.M., Francis, D.K., do Carmo Franco, M., Franco, O.H., Frontera, G., Fuchs, F.D., Fuchs, S.C., Fujita, Y., Furusawa, T., Gaciong, Z., Galvano, F., Garcia-de-la-Hera, M., Gareta, D., Garnett, S.P., Gaspoz, J.M., Gasull, M., Gates, L., Geleijnse, J.M., Ghasemian, A., Ghimire, A., Giampaoli, S., Gianfagna, F., Gill, T.K., Giovannelli, J., Goldsmith, R.A., Gonçalves, H., Gonzalez-Gross, M., González-Rivas, J.P., Gorbea, M.B., Gottrand, F., Graff-Iversen, S., Grafnetter, D., Grajda, A., Grammatikopoulou, M.G., Gregor, R.D., Grodzicki, T., Grøntved, A., Grosso, G., Gruden, G., Grujic, V., Gu, D., Guan, O.P., Gudmundsson, E.F., Gudnason, V., Guerrero, R., Guessous, I., Guimaraes, A.L., Gulliford, M.C., Gunnlaugsdottir, J., Gunter, M., Gupta, P.C., Gupta, R., Gureje, O., Gurzkowska, B., Gutierrez, L., Gutzwiller, F., Hadaegh, F., Halkjær, J., Hardy, R., Hari Kumar, R., Hata, J., Hayes, A.J., He, J., He, Y., Elisabeth, M., Henriques, A., Cadena, L.H., Herrala, S., Heshmat, R., Hihtaniemi, I.T., Ho, S.Y., Ho, S.C., Hobbs, M., Hofman, A., Dinc, G.H., Horimoto, ARVR, Hormiga, C.M., Horta, B.L., Houti, L., Howitt, C., Htay, T.T., Htet, A.S., Than Htike, M.M., Hu, Y., Huerta, J.M., Huisman, M., Husseini, A.S., Huybrechts, I., Hwalla, N., Iacoviello, L., Iannone, A.G., Ibrahim, M.M., Wong, N.I., Ikeda, N., Ikram, M.A., Irazola, V.E., Islam, M., Al-Safi Ismail, A., Ivkovic, V., Iwasaki, M., Jacobs, J.M., Jaddou, H., Jafar, T., Jamrozik, K., Janszky, I., Jasienska, G., Jelaković, A., Jelaković, B., Jennings, G., Jeong, S.L., Jiang, C.Q., Joffres, M., Johansson, M., Jokelainen, J.J., Jonas, J.B., Jørgensen, T., Joshi, P., Jóźwiak, J., Juolevi, A., Jurak, G., Jureša, V., Kaaks, R., Kafatos, A., Kajantie, E.O., Kalter-Leibovici, O., Kamaruddin, N.A., Karki, K.B., Kasaeian, A., Katz, J., Kauhanen, J., Kaur, P., Kavousi, M., Kazakbaeva, G., Keil, U., Boker, L.K., Keinänen-Kiukaanniemi, S., Kelishadi, R., Kemper, HCG, Kerimkulova, A., Kersting, M., Key, T., Khader, Y.S., Khalili, D., Khateeb, M., Khaw, K.T., Kiechl-Kohlendorfer, U., Kiechl, S., Killewo, J., Kim, J., Kim, Y.Y., Klumbiene, J., Knoflach, M., Kolle, E., Kolsteren, P., Korrovits, P., Koskinen, S., Kouda, K., Kowlessur, S., Koziel, S., Kriemler, S., Kristensen, P.L., Krokstad, S., Kromhout, D., Kruger, H.S., Kubinova, R., Kuciene, R., Kuh, D., Kujala, U.M., Kulaga, Z., Krishna Kumar, R., Kurjata, P., Kusuma, Y.S., Kuulasmaa, K., Kyobutungi, C., Laatikainen, T., Lachat, C., Lam, T.H., Landrove, O., Lanska, V., Lappas, G., Larijani, B., Laugsand, L.E., Le Nguyen Bao, K., Le, T.D., Leclercq, C., Lee, J., Lehtimäki, T., León-Muñoz, L.M., Levitt, N.S., Li, Y., Lilly, C.L., Lim, W.Y., Lima-Costa, M.F., Lin, H.H., Lin, X., Lind, L., Linneberg, A., Lissner, L., Litwin, M., Lorbeer, R., Lotufo, P.A., Lozano, J.E., Luksiene, D., Lundqvist, A., Lunet, N., Lytsy, P., Ma, G., Ma, J., Machado-Coelho, GLL, Machi, S., Maggi, S., Magliano, D.J., Magriplis, E., Majer, M., Makdisse, M., Malhotra, R., Mallikharjuna Rao, K., Malyutina, S., Manios, Y., Mann, J.I., Manzato, E., Margozzini, P., Marques-Vidal, P., Marques, L.P., Marrugat, J., Martorell, R., Mathiesen, E.B., Matijasevich, A., Matsha, T.E., Mbanya, JCN, Mc Donald Posso, A.J., McFarlane, S.R., McGarvey, S.T., McLachlan, S., McLean, R.M., McLean, S.B., McNulty, B.A., Mediene-Benchekor, S., Medzioniene, J., Meirhaeghe, A., Meisinger, C., Menezes, AMB, Menon, G.R., Meshram, I.I., Metspalu, A., Meyer, H.E., Mi, J., Mikkel, K., Miller, J.C., Minderico, C.S., Francisco, J., Miranda, J.J., Mirrakhimov, E., Mišigoj-Durakovic, M., Modesti, P.A., Mohamed, M.K., Mohammad, K., Mohammadifard, N., Mohan, V., Mohanna, S., Mohd Yusoff, M.F., Møllehave, L.T., Møller, N.C., Molnár, D., Momenan, A., Mondo, C.K., Monyeki, KDK, Moon, J.S., Moreira, L.B., Morejon, A., Moreno, L.A., Morgan, K., Moschonis, G., Mossakowska, M., Mostafa, A., Mota, J., Esmaeel Motlagh, M., Motta, J., Msyamboza, K.P., Mu, T.T., Muiesan, M.L., Müller-Nurasyid, M., Murphy, N., Mursu, J., Musil, V., Nabipour, I., Nagel, G., Naidu, B.M., Nakamura, H., Námešná, J., Nang, EEK, Nangia, V.B., Narake, S., Nauck, M., Navarrete-Muñoz, E.M., Ndiaye, N.C., Neal, W.A., Nenko, I., Neovius, M., Nervi, F., Nguyen, C.T., Nguyen, N.D., Nguyen, Q.N., Nguyen, Q.V., Nieto-Martínez, R.E., Niiranen, T.J., Ning, G., Ninomiya, T., Nishtar, S., Noale, M., Noboa, O.A., Noorbala, A.A., Norat, T., Noto, D., Al Nsour, M., O'Reilly, D., Oda, E., Oehlers, G., Oh, K., Ohara, K., Olinto, MTA, Oliveira, I.O., Omar, M.A., Onat, A., Ong, S.K., Ono, L.M., Ordunez, P., Ornelas, R., Osmond, C., Ostojic, S.M., Ostovar, A., Otero, J.A., Overvad, K., Owusu-Dabo, E., Paccaud, F.M., Padez, C., Pahomova, E., Pajak, A., Palli, D., Palmieri, L., Pan, W.H., Panda-Jonas, S., Panza, F., Papandreou, D., Park, S.W., Parnell, W.R., Parsaeian, M., Patel, N.D., Pecin, I., Pednekar, M.S., Peer, N., Peeters, P.H., Peixoto, S.V., Peltonen, M., Pereira, A.C., Peters, A., Petersmann, A., Petkeviciene, J., Pham, S.T., Pigeot, I., Pikhart, H., Pilav, A., Pilotto, L., Pitakaka, F., Piwonska, A., Plans-Rubió, P., Polašek, O., Porta, M., Portegies, MLP, Pourshams, A., Poustchi, H., Pradeepa, R., Prashant, M., Price, J.F., Puder, J.J., Puiu, M., Punab, M., Qasrawi, R.F., Qorbani, M., Bao, T.Q., Radic, I., Radisauskas, R., Rahman, M., Raitakari, O., Raj, M., Ramachandra Rao, S., Ramachandran, A., Ramos, E., Rampal, L., Rampal, S., Rangel Reina, D.A., Redon, J., Reganit, PFM, Ribeiro, R., Riboli, E., Rigo, F., Rinke de Wit, T.F., Ritti-Dias, R.M., Robinson, S.M., Robitaille, C., Rodríguez-Artalejo, F., Del Cristo Rodriguez-Perez, M., Rodríguez-Villamizar, L.A., Rojas-Martinez, R., Romaguera, D., Ronkainen, K., Rosengren, A., Roy, JGR, Rubinstein, A., Sandra Ruiz-Betancourt, B., Rutkowski, M., Sabanayagam, C., Sachdev, H.S., Saidi, O., Sakarya, S., Salanave, B., Salazar Martinez, E., Salmerón, D., Salomaa, V., Salonen, J.T., Salvetti, M., Sánchez-Abanto, J., Sans, S., Santos, D.A., Santos, I.S., Nunes Dos Santos, R., Santos, R., Saramies, J.L., Sardinha, L.B., Sarganas, G., Sarrafzadegan, N., Saum, K.U., Savva, S., Scazufca, M., Schargrodsky, H., Schipf, S., Schmidt, C.O., Schöttker, B., Schultsz, C., Schutte, A.E., Sein, A.A., Sen, A., Senbanjo, I.O., Sepanlou, S.G., Sharma, S.K., Shaw, J.E., Shibuya, K., Shin, D.W., Shin, Y., Si-Ramlee, K., Siantar, R., Sibai, A.M., Santos Silva, D.A., Simon, M., Simons, J., Simons, L.A., Sjöström, M., Skovbjerg, S., Slowikowska-Hilczer, J., Slusarczyk, P., Smeeth, L., Smith, M.C., Snijder, M.B., So, H.K., Sobngwi, E., Söderberg, S., Solfrizzi, V., Sonestedt, E., Song, Y., Sørensen, TIA, Soric, M., Jérome, C.S., Soumare, A., Staessen, J.A., Stathopoulou, M.G., Stavreski, B., Steene-Johannessen, J., Stehle, P., Stein, A.D., Stergiou, G.S., Stessman, J., Stieber, J., Stöckl, D., Stocks, T., Stokwiszewski, J., Stronks, K., Strufaldi, M.W., Sun, C.A., Sung, Y.T., Suriyawongpaisal, P., Sy, R.G., Shyong Tai, E., Tammesoo, M.L., Tamosiunas, A., Tan, E.J., Tang, X., Tanser, F., Tao, Y., Tarawneh, M.R., Tarqui-Mamani, C.B., Tautu, O.F., Taylor, A., Theobald, H., Theodoridis, X., Thijs, L., Thuesen, B.H., Tjonneland, A., Tolonen, H.K., Tolstrup, J.S., Topbas, M., Topór-Madry, R., Tormo, M.J., Torrent, M., Traissac, P., Trichopoulos, D., Trichopoulou, A., Trinh, OTH, Trivedi, A., Tshepo, L., Tulloch-Reid, M.K., Tullu, F., Tuomainen, T.P., Tuomilehto, J., Turley, M.L., Tynelius, P., Tzourio, C., Ueda, P., Ugel, E.E., Ulmer, H., Uusitalo, HMT, Valdivia, G., Valvi, D., van der Schouw, Y.T., Van Herck, K., Van Minh, H., van Rossem, L., Van Schoor, N.M., van Valkengoed, IGM, Vanderschueren, D., Vanuzzo, D., Vatten, L., Vega, T., Velasquez-Melendez, G., Veronesi, G., Monique Verschuren, W.M., Verstraeten, R., Victora, C.G., Viet, L., Viikari-Juntura, E., Vineis, P., Vioque, J., Virtanen, J.K., Visvikis-Siest, S., Viswanathan, B., Vlasoff, T., Vollenweider, P., Voutilainen, S., Wade, A.N., Wagner, A., Walton, J., Wan Bebakar, W.M., Wan Mohamud, W.N., Wanderley, R.S., Wang, M.D., Wang, Q., Wang, Y.X., Wang, Y.W., Wannamethee, S.G., Wareham, N., Wedderkopp, N., Weerasekera, D., Whincup, P.H., Widhalm, K., Widyahening, I.S., Wiecek, A., Wijga, A.H., Wilks, R.J., Willeit, J., Willeit, P., Williams, E.A., Wilsgaard, T., Wojtyniak, B., Wong-McClure, R.A., Wong, JYY, Wong, T.Y., Woo, J., Giwercman Wu, A., Wu, F.C., Wu, S., Xu, H., Yan, W., Yang, X., Ye, X., Yiallouros, P.K., Yoshihara, A., Younger-Coleman, N.O., Yusoff, A.F., Zainuddin, A.A., Zambon, S., Zampelas, A., Zdrojewski, T., Zeng, Y., Zhao, D., Zhao, W., Zheng, W., Zheng, Y., Zhu, D., Zhussupov, B., Zimmermann, E., Cisneros, J.Z., Zhou, Bin, Bentham, Jame, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M, Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charle, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, Jame, Bilano, Ver, Stevens, Gretchen A, Cowan, Melanie J, Riley, Leanne M, Chen, Zhengming, Hambleton, Ian R, Jackson, Rod T, Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K, Sorić, Maroje, Starc, Gregor, Sundström, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abu-Rmeileh, Niveen M, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A, Agyemang, Charle, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M, Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N, Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A, Ängquist, Lars H, Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assunção, Maria Cecília F, Avdicová, Mária, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V, Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Barbagallo, Carlo M, Barceló, Alberto, Barkat, Amina, Barros, Aluisio J D, Barros, Mauro V, Bata, Iqbal, Batieha, Anwar M, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Romdhane, Habiba Ben, Benet, Mikhail, Benson, Lowell S, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bi, Yufang, Bikbov, Mukharram, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Björkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G, Boissonnet, Carlos P, Bongard, Vanina, Borchini, Rossana, Bovet, Pascal, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M, Bruno, Graziella, Bueno-de-Mesquita, H B(as), Bugge, Anna, Burns, Con, Bursztyn, Michael, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Günay, Cândido, Ana Paula C, Capuano, Vincenzo, Cardoso, Viviane C, Carlsson, Axel C, Carvalho, Maria J, Casanueva, Felipe F, Casas, Juan-Pablo, Caserta, Carmelo A, Chamukuttan, Snehalatha, Chan, Angelique W, Chan, Queenie, Chaturvedi, Himanshu K, Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolore, Cho, Belong, Cho, Yumi, Christofaro, Diego G, Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, El, Concin, Han, Cooper, Cyru, Cooper, Rachel, Coppinger, Tara C, Costanzo, Simona, Cottel, Dominique, Cowell, Chri, Craig, Cora L, Crujeiras, Ana B, Cruz, Juan J, D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abba, Delisle, Hélène, Deschamps, Valérie, Dhana, Klodian, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soare, Diaz, Alejandro, Dickerson, Ty T, Do, Ha T P, Donfrancesco, Chiara, Donoso, Silvana P, Döring, Angela, Dorobantu, Maria, Doua, Kouamelan, Drygas, Wojciech, Dulskiene, Virginija, Džakula, Aleksandar, Dzerve, Vilni, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Elosua, Roberto, Erasmus, Rajiv T, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, Escobedo-de la Peña, Jorge, Evans, Alun, Faeh, David, Fall, Caroline H, Farzadfar, Farshad, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D, Fischer, Krista, Föger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M, Francis, Damian K, do Carmo Franco, Maria, Franco, Oscar H, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Galvano, Fabio, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M, Ghasemian, Anoosheh, Ghimire, Anup, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Goldsmith, Rebecca A, Gonçalves, Helen, Gonzalez-Gross, Marcela, González-Rivas, Juan P, Gorbea, Mariano Bonet, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G, Gregor, Ronald D, Grodzicki, Tomasz, Grøntved, Ander, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idri, Guimaraes, Andre L, Gulliford, Martin C, Gunnlaugsdottir, Johanna, Gunter, Marc, Gupta, Prakash C, Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Halkjær, Jytte, Hardy, Rebecca, Hari Kumar, Rachakulla, Hata, Jun, Hayes, Alison J, He, Jiang, He, Yuna, Elisabeth, Marleen, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C, Hobbs, Michael, Hofman, Albert, Dinc, Gonul Horasan, Horimoto, Andrea R V R, Hormiga, Claudia M, Horta, Bernardo L, Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Than Htike, Maung Maung, Hu, Yonghua, Huerta, José María, Huisman, Martijn, Husseini, Abdullatif S, Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G, Ibrahim, Mohsen M, Wong, Norazizah Ibrahim, Ikeda, Nayu, Ikram, M Arfan, Irazola, Vilma E, Islam, Muhammad, al-Safi Ismail, Aziz, Ivkovic, Vanja, Iwasaki, Masanori, Jacobs, Jeremy M, Jaddou, Hashem, Jafar, Tazeen, Jamrozik, Konrad, Janszky, Imre, Jasienska, Grazyna, Jelaković, Ana, Jelaković, Bojan, Jennings, Garry, Jeong, Seung-lyeal, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattia, Jokelainen, Jari J, Jonas, Jost B, Jørgensen, Torben, Joshi, Pradeep, Jóźwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Jureša, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O, Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Karki, Khem B, Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C G, Kengne, Andre P, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khateeb, Mohammad, Khaw, Kay-Tee, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M, Kulaga, Zbigniew, Krishna Kumar, R, Kurjata, Pawel, Kusuma, Yadlapalli S, Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E, Le Nguyen Bao, Khanh, Le, Tuyen D, Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimäki, Terho, León-Muñoz, Luz M, Levitt, Naomi S, Li, Yanping, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lar, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lorbeer, Roberto, Lotufo, Paulo A, Lozano, José Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L L, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Magriplis, Emmanuella, Majer, Marjeta, Makdisse, Marcia, Malhotra, Rahul, Mallikharjuna Rao, Kodavanti, Malyutina, Sofia, Manios, Yanni, Mann, Jim I, Manzato, Enzo, Margozzini, Paula, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mathiesen, Ellisiv B, Matijasevich, Alicia, Matsha, Tandi E, Mbanya, Jean Claude N, Mc Donald Posso, Anselmo J, McFarlane, Shelly R, McGarvey, Stephen T, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Mi, Jie, Mikkel, Kairit, Miller, Jody C, Minderico, Cláudia S, Francisco, Juan, Miranda, J Jaime, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Modesti, Pietro A, Mohamed, Mostafa K, Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Mohd Yusoff, Muhammad Fadhli, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Esmaeel Motlagh, Mohammad, Motta, Jorge, Msyamboza, Kelias P, Mu, Thet Thet, Muiesan, Maria L, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M, Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K, Nangia, Vinay B, Narake, Sameer, Nauck, Matthia, Navarrete-Muñoz, Eva Maria, Ndiaye, Ndeye Coumba, Neal, William A, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nguyen, Quang V, Nieto-Martínez, Ramfis E, Niiranen, Teemu J, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Parnell, Winsome R, Parsaeian, Mahboubeh, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Peeters, Petra H, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Pham, Son Thai, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Portegies, Marileen L P, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F, Puder, Jardena J, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A, Redon, Josep, Reganit, Paul Ferdinand M, Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Rinke de Wit, Tobias F, Ritti-Dias, Raphael M, Robinson, Sian M, Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S, Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A, Santos, Ina S, Nunes dos Santos, Renata, Santos, Rute, Saramies, Jouko L, Sardinha, Luis B, Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savva, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sharma, Sanjib K, Shaw, Jonathan E, Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöström, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C, Snijder, Marieke B, So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild I A, Soric, Maroje, Jérome, Charles Sossa, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G, Shyong Tai, E, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B, Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Torrent, Matie, Traissac, Pierre, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh T H, Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E, Ulmer, Hanno, Uusitalo, Hannu M T, Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M, van Valkengoed, Irene G M, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lar, Vega, Toma, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Monique Verschuren, W M, Verstraeten, Roosmarijn, Victora, Cesar G, Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N, Wagner, Aline, Walton, Janette, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley, Rildo S, Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Wedderkopp, Niel, Weerasekera, Deepa, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wijga, Alet H, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Emmanuel A, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Justin Y Y, Wong, Tien Yin, Woo, Jean, Giwercman Wu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yiallouros, Panayiotis K, Yoshihara, Akihiro, Younger-Coleman, Novie O, Yusoff, Ahmad Faudzi, Zainuddin, Ahmad Ali, Zambon, Sabina, Zampelas, Antoni, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Wei, Zheng, Yingfeng, Zhu, Dan, Zhussupov, Baurzhan, Zimmermann, Esther, Cisneros, Julio Zuñiga, The State Key Laboratory of Cell Biology [Shanghai, China] (CAS Center for Excellence in Molecular Cell Science), Shanghai Institute of Biochemistry and Cell Biology [Shanghai, China]-University of Chinese Academy of Sciences [Shanghai, China], Imperial College London, University of Kentucky, Middlesex University, Cleveland Clinic, Universidad Peruana Cayetano Heredia (UPCH), Brandeis University, Mulago Hospital [Kampala, Ouganda], Department of Epidemiology and Public Health, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organisation (WHO), Al-Quds University, Discipline of Medicine, University of South Australia [Adelaide], Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Centre for Industrial Management, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Preventive Medicine, Copenhagen University Hospitals, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Dept. Atherosclerose, University of Iceland [Reykjavik], Institute for Biotechnology and Bioengineering (IBB), Technical University of Lisbon, Medical University of Łódź (MUL), Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid (UAM), Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Sunder Lal Jain Hospital, Ufa Eye Research Institute [Bashkortostan], National Institute of Public Health, Department of Epidemiology, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association-Leibniz Association, CHU Toulouse [Toulouse], Institute of Social and Preventive Medicine, Lausanne university hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), ASU - School for Engineering of Matter, Transport and Energy, Arizona State University [Tempe] (ASU), Universidade do Porto = University of Porto, University of Oxford [Oxford], Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), 2nd Department of Internal Medicine, Molecular Medicine, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-IRC KULAK, Department of Public Health, State University of Ghent, MRC Lifecourse Epidemiology Unit [Southampton, UK], University of Southampton, Réseau International des Instituts Pasteur (RIIP), Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Sahlgrenska University Hospital [Gothenburg], Institute of Metabolic Science, MRC, Institut National de Nutrition et de Technologie Alimentaire (INNTA), University of Huddersfield, IMIM-Hospital del Mar, Generalitat de Catalunya, Medstar Research Institute, Queen's University [Belfast] (QUB), Medical Research Council, Applied Sciences, National Research Institute on Food and Nutrition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Innsbruck Medical University [Austria] (IMU), Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Laboratoire d'Etude des Mammifères Marins (LEMM), Océanopolis [Brest], Faculté de Médecine Henri Warembourg - Université de Lille, Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark (SDU), Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Centro Investig Quim Aplicada, Coahuila, Mexico, Centro Investigacion en Quimica Aplicada, Coahuila, Mexico, University of Geneva [Switzerland], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], Health Services Research Unit, Danish Cancer Society, Institute of Cancer Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), University College of London [London] (UCL), The Georges Institute for International Health, The University of Sydney, School of Information Technology, Deakin University Waurn Ponds, Faculté de Médecine, Université Djilali Liabès [Sidi-Bel-Abbès], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), VU University Medical Center [Amsterdam], Universiteit Gent = Ghent University [Belgium] (UGENT), Faculty of Agricultural and Food Science, American University of Beirut [Beyrouth] (AUB), Åbo Akademi University [Turku], Department of Public Health Sciences, Karolinska Institutet [Stockholm], Great Lakes Institute for Environmental Research, University of Windsor [Ca], Universität Heidelberg [Heidelberg], Research Center for Prevention and Health, University of Ljubljana, Division of Cancer Epidemiology, University of Crete School of medicine, School of Public Health and Clinical Nutrition, University of Eastern Finland, Institute of Epidemiology and Social Medicine, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Research Institute of Child Nutrition Dortmund, Rheinische Friedrich-Wilhelms-Universität Bonn, Cancer Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Oncology, University of Tampere Medical School, University of Tampere, Wageningen University and Research [Wageningen] (WUR), Centre for Environmental Health, National Institue of Public Health, School of Public Health, The University of Hong Kong (HKU), Tehran University of Medical Sciences, Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN), INRAN, National University of Singapore (NUS), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Uppsala Universitet [Uppsala], Department of Public Health and Community Medicine, University of Gothenburg (GU), Institute of Earthquake Science, CEA, Beijing, CEA, Beijing, University of Porto Medical School, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aging Program, National research council, Padua, Italy, Baker IDI Heart and Diabetes Institute, Institute of Internal Medicine, Russian Academy of Medical Sciences, Department of Nutrition and Dietetics, Harokopio University, Emory University [Atlanta, GA], Départment of Biotechnology, Faculty of Science, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tartu, Department of Community, Université Ain Shams-Faculty of Medicine-Environmental and Occupational Medicine, Pécsi Tudemányegyetem, Department of Community, Environmental and Occupational Medicine, Université Ain Shams, Research Centre in Physical Activity, Health and Leisure, Nutrition and Metabolism Section, International Agency for Research on Cancer, Bushehr University of Medical Sciences, Institute of Epidemiology and Medical Biometry [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Università degli studi di Palermo - University of Palermo, MRc Environmental Epidemiology Unit, Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Department of Epidemiology and Population Studies, Jagiellonian University, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Social Robotics Laboratory, University of Freiburg, Freiburg im Breisgau, Department of Ophthalmology, Universitätsklinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, University of Bari Aldo Moro (UNIBA), Department of Cardiology, Eastbourne General Hospital, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), King‘s College London, Public Health Sciences, University of Edinburgh, Movement Disorders and Tourette Centre, Genetica medicala, Victor Babeş University of Medicine and Pharmacy (UMFT), Andrology Unit, United Laboratories of Tartu University Clinics, Tampere University Hospital, Department of Hygiene and Epidemiology, Dept of Epidemiology and Public Health, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Institut de Veille Sanitaire (INVS), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], University of São Paulo (USP), Institut de Recherche pour le Développement (IRD [France-Sud]), Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Department of Reproductive Endocrinology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC - Academic medical center, Central Hospital and Faculty of medicine and biomedical sciences university, University of Yaoundé [Cameroun], Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, School of Computing [Leeds], University of Leeds, Copenhagen University Hospital, Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maastricht University [Maastricht], Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Applied Food Science, Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, University of Amsterdam, Dept. of Social Medecine, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Africa Centre for Health and Population Studies, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-Medical Research Council of South Africa, Center for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Department of Cardiovascular Sciences [Leuven], Cancer Epidemiology Institute, Department of Epidemiology and Health Promotion (MONICA Data Centre), National Public Health Institute, Nutrition et Alimentation des Populations aux Suds (NutriPass), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Havard School of Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], University of Kuopio, Tampere University, University Medical Centre Utrecht, Department of Social Medicine, Amsterdam, Center for Metabolic Bone Diseases, Catholic University of Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Universidad Miguel Hernández [Elche] (UMH), Institute of Public Health and Clinical Nutrition [Kuopio, Finland], Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Division of Community Health Sciences, St George's University of London, Medizinische Universität Wien = Medical University of Vienna, Medical University of Silesia (SUM), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Innsbruck, National Institute of Hygiene Warsaw, Johns Hopkins University School of Medicine [Baltimore], Food Science and Technology, Beijing Forestry University, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics (CAE-NUAA), NUAA, Chinese Center for Disease Control and Prevention, Department of Applied Mathematics, School of Science, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, Siemens Corporate Research, Siemens AG [Munich], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), This work was supported by the Wellcome Trust [101506/Z/13/Z]., NCD Risk Factor Collaboration (NCD-RisC). We thank WHO country and regional offices and the World Heart Federation for support in data identification and access., Universidad Autonoma de Madrid (UAM), University of Turin, Universidade do Porto, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Lille 2 - Faculté de Médecine, Westfälische Wilhelms-Universität Münster (WWU), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa, Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Lund University Diabetes Centre-Lund University [Lund], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Medical University of Silesia, Katowice, Apollo - University of Cambridge Repository, University of Kentucky (UK), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lausanne University Hospital, University of Oxford, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université de Genève = University of Geneva (UNIGE), Deakin University [Waurn Ponds], Universiteit Gent = Ghent University (UGENT), Universität Heidelberg [Heidelberg] = Heidelberg University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Universidade de São Paulo = University of São Paulo (USP), Lund University [Lund], Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Yiallouros, Panayiotis K. [0000-0002-8339-9285], Giampaoli, Simona [0000-0002-6679-1488], Moschonis, George [0000-0003-3009-6675], Papandreou, Dimitrios [0000-0002-4923-484X], Stathopoulou, Maria G. [0000-0003-4376-2083], Stergiou, George S. [0000-0002-6132-0038], Trichopoulou, Antonia [0000-0002-7204-6396], Valvi, Damaskini [0000-0003-4633-229X], Chen, Z, Woodward, M, Key, T, and Smith, M
Subjects: systolic blood pressure, Settore MED/09 - Medicina Interna, blood pressure measurement, HEALTH EXAMINATION SURVEYS, Blood Pressure, Hypertension, Population Health, Global Health, Non-communicable Disease, Epidemiology, [SDV]Life Sciences [q-bio], global health, South Asia, purl.org/pe-repo/ocde/ford#3.03.09 [https], kohonnut verenpaine, Medicine and Health Sciences, middle income country, measurement method, skin and connective tissue diseases, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771, Public, Environmental & Occupational Health, adult, Population health, public health, blood pressure regulation, Public Health, Global Health, Social Medicine and Epidemiology, Non-communicable disease, kansainvälinen vertailu, health survey, aged, female, priority journal, Blood pressure, mean arterial pressure, GLOBAL TRENDS, SODIUM-INTAKE, Life Sciences & Biomedicine, survey design, hypertension, prevalence, Global health, UNITED-STATES, URBAN COMMUNITIES, Article, SECULAR TRENDS, Middle East, Central Asia, male, disease prevalence, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, kansanterveys, blood, SYSTEMATIC ANALYSIS, human, verenpainetauti, non-communicable disease, Science & Technology, Pacific Ocean, high income country, diastolic blood pressure, Pacific Rim, Blood Pressure - Epidemiology - Population, North Africa, major clinical study, HYPERTENSION PREVALENCE, verenpaine, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, ARTERIAL-HYPERTENSION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, POTASSIUM INTAKE, sense organs, trend analysis, trend study, population research, population health, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, low income country
Abstract: Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups., This work was supported by the Wellcome Trust [101506/Z/13/Z].
Published: 2018

41. Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study

Author: Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Peeters, Petra H., Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J., Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay Tee, Wareham, Nick, Bradbury, Kathryn E., Perez-Cornago, Aurora, Tsilidis, Konstantinos K., Ferrari, Pietro, Riboli, Elio, Gunter, Marc J., Touvier, Mathilde, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition and Metabolism Section, International Agency for Research on Cancer, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Cancer Registry of Norway, Institute of Population-Based Cancer Research, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Public Health, Section for Epidemiology, Aarhus University [Aarhus], Danish Cancer Society Research Center, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition (DIfE), WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Cancer registry and histopathology unit, Civile - M.P.Arezzo Hospital, Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital-Center for Cancer Prevention (CPO-Piemonte), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], School of Public Health - Department of Epidemiology and Biostatistics, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Julius Center for Health Sciences and Primary Care, Department of Nutrition [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Public Health Directorate Asturias, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L´Hospitallet de Llobregat, Facultat de Ciències de la Salut Blanquerna, Universitat Ramon Llull [Barcelona] (URL), Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Public Health Institute of Navarra, IdiSNA, Navarra Institute for Health Research, Public Health Department of Gipuzkoa, Diabetes and Cardiovascular disease, Genetic Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Nutritional Epidemiology, Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy, University of Gothenburg (GU), Department of Odontology, Umeå University, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, Institute of Metabolic Science, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, French National Cancer Institute (INCa)-Canceropole Ile-de-France [2017-1-PL SHS-01-INSERM ADR 5-1], European Commission (DG-SANCO), Danish Cancer Society (Denmark), Ligue Contre le Cancer, (France), Institut Gustave Roussy, (France), Mutuelle Generale de l'Education Nationale, (France), Institut National de la Sante et de la Recherche Medicale (Inserm), (France), Deutsche Krebshilfe (Germany), Deutsches Krebsforschungszentrum (Germany), Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Dutch Ministry of Public Health, Welfare, and Sports (VWS) (the Netherlands), Netherlands Cancer Registry (NKR) (the Netherlands), LK Research Funds (the Netherlands), Dutch Prevention Funds (the Netherlands), Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands), World Cancer Research Fund (WCRF) (the Netherlands), Statistics Netherlands (the Netherlands), Health Research Fund (FIS) [PI13/00061], Regional Government of Andalucia (Spain), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) [6236], Regional Government of Navarra, ISCIII RETIC (Spain) [RD06/0020], Swedish Cancer Society (Sweden), Swedish Scientific Council (Sweden), County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK [14136, C570/A16491, C8221/A19170], Medical Research Council [1000143, MR/M012190/1], National Research Council (Italy), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Hôpital avicenne, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), 'CIVIC-M.P. AREZZO' Hospital, University of Oxford, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Deschasaux, Mélanie [0000-0002-3359-420X], Huybrechts, Inge [0000-0003-3838-855X], Murphy, Neil [0000-0003-3347-8249], Hercberg, Serge [0000-0002-3168-1350], Srour, Bernard [0000-0002-1277-3380], Kesse-Guyot, Emmanuelle [0000-0002-9715-3534], Weiderpass, Elisabete [0000-0003-2237-0128], Dahm, Christina C [0000-0003-0481-2893], Kyrø, Cecilie [0000-0002-9083-8960], Olsen, Anja [0000-0003-4788-503X], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Mahamat-Saleh, Yahya [0000-0002-5892-8886], Tumino, Rosario [0000-0003-2666-414X], Sacerdote, Carlotta [0000-0002-8008-5096], Hjartåker, Anette [0000-0003-3002-4030], Skeie, Guri [0000-0003-2476-4251], Jakszyn, Paula [0000-0003-0672-8847], Huerta, José María [0000-0002-9637-3869], Sonestedt, Emily [0000-0002-0747-4562], Johansson, Ingegerd [0000-0002-9227-8434], Wareham, Nick [0000-0003-1422-2993], Bradbury, Kathryn E [0000-0003-3345-7333], Perez-Cornago, Aurora [0000-0002-5652-356X], Riboli, Elio [0000-0001-6795-6080], Touvier, Mathilde [0000-0002-8322-8857], Apollo - University of Cambridge Repository, Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C, Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Luka, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Ba, Peeters, Petra H, Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J, Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Perez-Cornago, Aurora, Tsilidis, Konstantinos K, Ferrari, Pietro, Riboli, Elio, Gunter, Marc J, and Touvier, Mathilde
Subjects: Adult, Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nutrition Policy, Cohort Studies, Food Preferences, Medicine, General & Internal, project, Food Labeling, Risk Factors, front-of-package, su.vi.max cohort, General & Internal Medicine, Neoplasms, Humans, french adults, Prospective Studies, dietary index, database, Medicine(all), validation, Nutrition and Dietetics, Science & Technology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, 11 Medical And Health Sciences, Middle Aged, Näringslära, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Europe, prospective association, 3121 General medicine, internal medicine and other clinical medicine, Medicine, Female, cardiovascular-disease risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Life Sciences & Biomedicine, Nutritive Value, france, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Source at https://doi.org/10.1371/journal.pmed.1002651. Background - Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. Methods and findings - This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992–2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03–1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. Conclusions - In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
Published: 2018

42. Mechanistic insights into the detection of free fatty and bile acids by ileal glucagon-like peptide-1 secreting cells

Author: Goldspink, Deborah, Lu, Van, Billing, Lawrence, Larraufie, Pierre, Tolhurst, Gwen, Gribble, Fiona, Reimann, Frank, Wellcome Trust-MRC Institute of Metabolic Science, Lu, Van [0000-0002-4880-6455], Larraufie, Pierre [0000-0001-7718-6200], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], and Apollo - University of Cambridge Repository
Subjects: Organoid, lcsh:Internal medicine, Enteroendocrine Cells, Fatty Acids, Diabetes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, FFA1, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Membrane Potentials, Receptors, G-Protein-Coupled, Bile Acids and Salts, Mice, Glucagon-Like Peptide 1, Ileum, GPBAR1, Animals, Original Article, Calcium, Obesity, lcsh:RC31-1245, GLP-1, Cells, Cultured, TRPC Cation Channels
Abstract: Objectives The aim of this study was to investigate the electrical properties of ileal Glucagon-like peptide 1 (GLP-1) secreting L-cells using murine organoid cultures and the electrophysiological and intracellular signaling pathways recruited following activation of the Gαq-coupled free fatty acid receptors FFA1 and Gαs-coupled bile acid receptors GPBAR1. Methods Experiments were performed using ileal organoids generated from mice transgenically expressing fluorescent reporters (Epac2-camps and GCaMP3) under control of the proglucagon promoter. Electrophysiology and single cell imaging were performed on identified L-cells in organoids, and GLP-1 secretion from cultured organoids was measured by immunoassay. Results The FFA1 ligand TAK-875 triggered L-cell electrical activity, increased intracellular calcium, and activated a depolarizing current that was blocked by the TRPC3 inhibitor Pyr3. TAK-875 triggered GLP-1 secretion was Pyr3 sensitive, suggesting that the TRPC3 channel links FFA1 activation to calcium elevation and GLP-1 release in L-cells. GPBAR1 agonist triggered PKA-dependent L-type Ca2+ current activation and action potential firing in L-cells. The combination of TAK-875 and a GPBAR1 agonist triggered synergistic calcium elevation and GLP-1 secretory responses. Conclusions FFA1 and GPBAR1 activation individually increased electrical activity in L-cells by recruiting pathways that include activation of TRPC3 and L-type voltage-gated Ca2+ channels. Synergy between the pathways activated downstream of these receptors was observed both at the level of Ca2+ elevation and GLP-1 secretion., Graphical abstract, Highlights • Organoid-derived ileal L-cells recapitulate the properties of primary ileal L-cells. • GPBAR1 agonism stimulates L-type Ca2+ current-dependent action potentials in L-cells. • FFA1 agonists depolarize L-cells via TRPC3 activation. • Synergy between GPBAR1/FFA1 occurs at the levels of Ca2+ responses and secretion.
Published: 2018

43. Liquid chromatography/mass spectrometry based detection and semi-quantitative analysis of INSL5 in human and murine tissues

Author: Kay, R.G., Galvin, S., Larraufie, P., Reimann, F., Gribble, F.M., and Wellcome Trust-MRC Institute of Metabolic Science
Subjects: [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
Abstract: International audience; Insulin-like peptide 5 (INSL5) is a hormone produced by enteroendocrine L-cells in the colon that has recently been implicated in the control of metabolic homeostasis. However, research into its physiology has been hindered by the reported unreliability of commercially available immunoassays and additional detection assays would benefit this emerging field. Methods: Peptides from purified murine L-cells and homogenates from both human and mouse colonic tissues were extracted by precipitating larger proteins with acetonitrile. Untargeted liquid chromatography/tandem mass spectrometry (LC/MS/MS) analyses, followed by database searching, were used to detect and identify various INSL5 gene derived peptides and characterise their precise sequence. A similar approach was developed to quantify INSL5 levels in primary intestinal culture supernatants after purification and concentration by solid-phase extraction. Results: Mass spectral analysis of purified enteroendocrine cells and tissue homogenates identified the exact sequence of A and B chains of INSL5 endogenously expressed in L-cells. Differences in the endogenously processed peptide and the Swissprot database entry were observed for murine INSL5, whereas the human sequence matched previous predictions from heterologous expression experiments. INSL5 was detected in the supernatant of human and mouse primary colonic cultures and concentrations increased after treatment with a known L-cell stimulus. Conclusions: The first LC/MS/MS-based method capable of the detection and semiquantitative analysis of endogenous INSL5 using MS-based techniques has been demonstrated. The methodology will enable the identification of stimulants for INSL5 secretion from murine and human primary colonic epithelial cultures.
Published: 2017

44. Editorial: Are Rodent Models Fit for Investigation of Human Obesity and Related Diseases?

Author: Patrick C. Even, Gilles Fromentin, Robert K. Semple, Nicholas M. Morton, Sam Virtue, Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp,Addenbrookes Treatment Ctr, Université de Cambridge, Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge [UK] (CAM), and Institut National de la Recherche Agronomique (INRA)-AgroParisTech
Subjects: 0301 basic medicine, obesity, Rodent, type 2 diabetes mellitus, Endocrinology, Diabetes and Metabolism, education, lcsh:TX341-641, Disease, 030204 cardiovascular system & hematology, Bioinformatics, T2DM - Type 2 Diabetes mellitus, 03 medical and health sciences, 0302 clinical medicine, biology.animal, parasitic diseases, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], health care economics and organizations, ComputingMilieux_MISCELLANEOUS, Human obesity, Nutrition, disease, Nutrition and Dietetics, biology, business.industry, Type 2 Diabetes Mellitus, non-alcoholic fatty liver disease, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Obesity, rodent models, 3. Good health, 030104 developmental biology, Editorial, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, lcsh:Nutrition. Foods and food supply, Food Science
Abstract: Editorial on the Research Topic: Are Rodent Models Fit for Investigation of Human Obesity and Related Diseases? This article was submitted to Clinical Nutrition, a section of the journal Frontiers in Nutrition; International audience
Published: 2017

45. The SNARE Protein Syntaxin-1a Plays an Essential Role in Biphasic Exocytosis of the Incretin Hormone Glucagon-Like Peptide 1

Author: Yasaman Nahaei, Fiona M. Gribble, Sarah E. Wheeler, Alexandre B. Hardy, Pierre Larraufie, Holly M. Stacey, Frank Reimann, Herbert Y. Gaisano, Stephen J. Hale, Patricia L. Brubaker, and Wellcome Trust-MRC Institute of Metabolic Science
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, endocrine system, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Enteroendocrine Cells, Incretin, Syntaxin 1, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Exocytosis, Article, 03 medical and health sciences, chemistry.chemical_compound, Mice, Glucagon-Like Peptide 1, Ileum, Internal medicine, Internal Medicine, medicine, Animals, Secretion, Obesity, Dipeptidyl peptidase-4, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Forskolin, Insulin, digestive, oral, and skin physiology, Glucagon-like peptide-1, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Glucose, chemistry, Diabetes Mellitus, Type 2, Gene Expression Regulation, Female, Hormone
Abstract: Exocytosis of the hormone glucagon-like peptide 1 (GLP-1) by the intestinal L cell is essential for the incretin effect after nutrient ingestion and is critical for the actions of dipeptidyl peptidase 4 inhibitors that enhance GLP-1 levels in patients with type 2 diabetes. Two-photon microscopy revealed that exocytosis of GLP-1 is biphasic, with a first peak at 1–6 min and a second peak at 7–12 min after stimulation with forskolin. Approximately 75% of the exocytotic events were represented by compound granule fusion, and the remainder were accounted for by full fusion of single granules under basal and stimulated conditions. The core SNARE protein syntaxin-1a (syn1a) was expressed by murine ileal L cells. At the single L-cell level, first-phase forskolin-induced exocytosis was reduced to basal (P < 0.05) and second-phase exocytosis abolished (P < 0.05) by syn1a knockout. L cells from intestinal-epithelial syn1a–deficient mice demonstrated a 63% reduction in forskolin-induced GLP-1 release in vitro (P < 0.001) and a 23% reduction in oral glucose–stimulated GLP-1 secretion (P < 0.05) in association with impairments in glucose-stimulated insulin release (by 60%; P < 0.01) and glucose tolerance (by 20%; P < 0.01). The findings identify an exquisite mechanism of metered secretory output that precisely regulates release of the incretin hormone GLP-1 and hence insulin secretion after a meal.
Published: 2017

46. Angiotensin II Type 1 Receptor-Dependent GLP-1 and PYY Secretion in Mice and Humans

Author: Pais, Ramona, Rievaj, Juraj, Larraufie, Pierre, Gribble, Fiona, Reimann, Frank, Larraufie, Pierre [0000-0001-7718-6200], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], Apollo - University of Cambridge Repository, and Wellcome Trust-MRC Institute of Metabolic Science
Subjects: Male, Colon, Angiotensin II, Enteroendocrine Cells, Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Water-Electrolyte Balance, Receptor, Angiotensin, Type 1, Mice, Inbred C57BL, Renin-Angiotensin System, Glucagon-Like Peptide 1, Animals, Humans, Female, Peptide YY, Calcium Signaling, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, hormones, hormone substitutes, and hormone antagonists
Abstract: Angiotensin II (Ang II) is the key hormone mediator of the renin angiotensin system, which regulates blood pressure and fluid and electrolyte balance in the body. Here we report that in the colonic epithelium, the Ang II type 1 receptor is highly and exclusively expressed in enteroendocrine L cells, which produce the gut hormones glucagon-like peptide-1 and peptide YY (PYY). Ang II stimulated glucagon-like peptide-1 and PYY release from primary cultures of mouse and human colon, which was antagonized by the specific Ang II type 1 receptor blocker candesartan. Ang II raised intracellular calcium levels in L cells in primary cultures, recorded by live-cell imaging of L cells specifically expressing the fluorescent calcium sensor GCaMP3. In Ussing chamber recordings, Ang II reduced short circuit currents in mouse distal colon preparations, which was antagonized by candesartan or a specific neuropeptide Y1 receptor inhibitor but insensitive to amiloride. We conclude that Ang II stimulates PYY secretion, in turn inhibiting epithelial anion fluxes, thereby reducing net fluid secretion into the colonic lumen. Our findings highlight an important role of colonic L cells in whole-body fluid homeostasis by controlling water loss through the intestine.
Published: 2016
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47. Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change

Author: Giovanna Tagliabue, Ingegerd Johansson, José María Huerta, Domenico Palli, Anne Tjønneland, Petra H.M. Peeters, Aurelio Barricarte, Anne M. May, Göran Hallmans, Francesca L. Crowe, Madlen Schütze, Daphne L. van der A, Françoise Clavel-Chapelon, Birgit Teucher, George Makrygiannis, Thorkild I. A. Sørensen, Jonas Manjer, Isabelle Romieu, Laudina Rodríguez, H. B. Bueno-de-Mesquita, Veronique Chajes, Kim Overvad, Guy Fagherazzi, Nadia Slimani, Karen Margrete Due, Nicholas J. Wareham, Dimosthenis Zylis, Heiner Boeing, Pilar Amiano, Kay-Tee Khaw, Claus Dethlefsen, Amalia Mattiello, Marianne Uhre Jakobsen, Rudolf Kaaks, Jytte Halkjær, Marie-Christine Boutron-Ruault, Elisabet Wirfält, Esther Molina-Montes, Noémie Travier, Elio Riboli, Antonia Trichopoulou, [Jakobsen,MU] Department of Clinical Epidemiology. [Jakobsen,MU, Dethlefsen,C, Due,KM, Overvad,K] Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg. [Jakobsen,MU, Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Slimani,N, Chajès,V, Romieu,I] Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [May,AM, Peeter,PHM] Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht. [May,AM, van der A,DL, Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Sørensen,TIA] Institute of Preventive Medicine, Copenhagen University Hospital. [Halkjær,J, Tjønneland,A] The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M, Fagherazzi,G] Inserm, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy. Paris South University, Villejuif, France. [Teucher,B, Kaaks,R] German Cancer Research Center, Department of Cancer Epidemiology, Heidelberg. [Boeing,H, Schütze,M, Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Zylis,D] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School. [Trichopoulou,A, Zylis,D, Makrygiannis,G] Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples. [Tagliabue,G] Cancer Registry and Environmental Epidemiology Division, National Cancer Institute, Milan, Italy. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands. [Rodríguez,L] Public Health and Participation Directorate, Health and Health Care Services Council, Asturias. [Travier,N] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, IDIBELL, Barcelona. [Molina-Montes,E] Andalusian School of Public Health, Granada. [Molina-Montes,E, Huerta,JM, Barricarte,A, Amiano,P] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia. [Barricarte,A] Public Health Institute of Navarra, Pamplona. [Amiano,P] Public Health Division of Gipuzkoa, Basque Government, Spain. [Manjer,J] Department of Surgery, Skåne University Hospital Malmö, Lund University. [Wirfält,E] Department of Clinical Sciences in Malmö/Nutrition Epidemiology, Lund University, Malmö. [Johansson,I] Department of Odontology, Umeå University. [Hallmans,G] Department of Public Health and Clinical Medicine, Umeå University, Nutritional Research, Umeå, Sweden. [Khaw,K] Clinical Gerontology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge. [Wareham, NJ] MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge. [Crowe,F] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford. [Riboli,E, Peeters, PHM] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK., This work is part of the project Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of Home and Obesity (PANACEA), which is supported by the European Union in the framework of the Public Health Programmme (Contract 2005328). The work was further supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, Research Directorate-General 2005, Ligue contre le Cancer, Société 3M, Mutuelle Générale de l’Education Nationale, Institut National de la Santé de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany), Danish Cancer Society (Denmark), ISCIII (RETICC RD06/0020) of the Spanish Ministry of Health, the participating regional governments and institutions (Spain), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, The Wellcome Trust (UK), Greek Ministry of Health, Greek Ministry of Education, Hellenic Ministry of Health, Stavros Niarchos Foundation, and the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch Zorg Onderzoek Nederland (ZON), World Cancer Research Fund (WCRF) (The Netherlands), and and Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Västerbotten (Sweden). This work is also part of the project Hepatic and Adipose Tissue and Functions in the Metabolic Syndrome (HEPADIP, www.hepadip.org), which is supported by the European Commission as an Integrated Project under the 6th Framework Programme (Contract LSHM-CT-2005-018734) and part of the research program of the Danish Obesity Research Centre (DanORC, www.danorc.dk), which is supported by the Danish Council for Strategic Research (Contract 2101-06-0005).
Subjects: Male, Health (social science), 030309 nutrition & dietetics, Obesidad, Ácidos grasos omega-3, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, 0302 clinical medicine, Estudios prospectivos, Fosfolípidos, Modelos lineales, Prospective Studies, Masculino, Prospective cohort study, Phospholipids, chemistry.chemical_classification, 0303 health sciences, education.field_of_study, Weight change, Femenino, Middle Aged, n-3 fatty acids, Humanos, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Female, Original Article, lipids (amino acids, peptides, and proteins), Cohort study, Polyunsaturated fatty acid, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Phospholipid, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, 03 medical and health sciences, Chemicals and Drugs::Lipids::Fats::Dietary Fats::Dietary Fats, Unsaturated::Fatty Acids, Omega-3 [Medical Subject Headings], Physiology (medical), Internal medicine, Fatty Acids, Omega-3, Omega-3 fatty acids, medicine, Humans, Obesity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Linear Models [Medical Subject Headings], Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings], education, Mediana edad, business.industry, Body Weight, Peso corporal, Body weight, Confidence interval, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Endocrinology, Check Tags::Female [Medical Subject Headings], chemistry, Linear Models, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight [Medical Subject Headings], sense organs, business
Abstract: Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population. Yes
Published: 2016

48. Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study

Author: Per Magne Ueland, Anne Tjønneland, Nicholas J. Wareham, Petra H.M. Peeters, Richard Palmqvist, Stein Emil Vollset, Marc J. Gunter, Kim Overvad, Miren Dorronsoro, Amanda J. Cross, Giovanna Masala, J. Ramón Quirós, Øivind Midttun, Krasimira Aleksandrova, Dimitrios Trichopoulos, Aurelio Barricarte, Yunxia Lu, Ruth C. Travis, Bas Bueno-de-Mesquita, Tilman Kuehn, Shu Chun Chuang, Claudia Agnoli, José María Huerta, Tobias Pischon, Martin Lajous, Heiner Boeing, Marie-Christine Boutron-Ruault, Pagona Lagiou, Antonia Trichopoulou, Guy Fagherazzi, Rosario Tumino, Rudolf Kaaks, Kay-Tee Khaw, Amalia Mattiello, Antonio Agudo, Esther Molina-Montes, Dagmar Drogan, Elisabete Weiderpass, Paolo Vineis, Elio Riboli, Ingrid Ljuslinder, University Medical Center Utrecht, Imperial College Trust, [Chuang,S] Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.[Chuang,S, Bueno-de-Mesquita,B, Peeter,PH, Gunter,M, Lu,Y, Cross,AJ, Riboli,E, Vineis,P] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Vollset,SE] Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. Division of Epidemiology, Norwegian Institute of Public Health, Bergen, Norway. [Midttun,O] Bevital AS, Bergen, Norway. [Ueland,PM] Department of Clinical Science, University of Bergen, Bergen, Norway. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. [Bueno-de-Mesquita,B] The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Lajous,M, Fagherazzi,G, Boutron-Ruault,M] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. University of Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Küehn,T] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Drogan,D] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Oviedo, Spain. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Molina-Montes,E, Huerta,JM] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Travis,RC, Trichopoulou,A] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, ASP Ragusa, Italy. [Mattiello,A] Dipartamento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Palmqvist,R] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Aleksandrova,K] Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany., The EPIC cohort is supported by the Europe Against Cancer Program of the European Commission (SANCO). The individual centers also received funding from: Denmark: Danish Cancer Society, France: Ligue centre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), Greece: the Hellenic Health Foundation, the Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity, Germany : German Cancer Aid, and Federal Ministry of Education and Research, Italy: Italian Association for Research on Cancer and the National Research Council, The Netherlands: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, Norway: Helga – Nordforsk centre of excellence in food, nutrition and health and The Norwegian Extra Foundation for Health and Rehabilitation, The Norwegian Cancer Society, Spain: Health Research Fund (FIS) of the Spanish Ministry of Health (Exp 96/0032, RETICC DR06/ 0020), the Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (N0 6236), and the Navarra and the Catalan Institute of Oncology, Sweden: Swedish Cancer Society, Swedish Scientific Council, and Regional Governments of Skane and Västerbotten, UK: Cancer Research UK and Medical Research Council. Grant supports for the biochemical measurements: HDL-C and TG were analysed with additional support from the Ministry of Public Health, Welfare and Sports, the Netherlands,German Cancer Aid, Federal Ministry for Education and Research, European Union, European Union and AIRC-ITALY , German Cancer Aid, Federal Ministry for Education and Research, European Union, Stavros Niarchos Foundation , Hellenic Ministry of Health, Hellenic Health Foundation, MRC and Cancer Research UK, and Hba1c was analysed with additional support from National Cancer Institute grant 1RO1CA102460 and data analyses on CRP were performed with support from World Cancer Research Fund International and Wereld Kanker Onderzoek Fonds (WCRF NL)
Subjects: 0301 basic medicine, Aging, Síndrome metabòlica, Geriatrics & Gerontology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Methods::Research Design [Medical Subject Headings], 030204 cardiovascular system & hematology, Cardiovascular, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, GENETIC-VARIANTS, Hyperlipidemia, HORDALAND HEALTH, Metabolic syndrome, Cell-mediated immunity, Neopterin, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes [Medical Subject Headings], 3. Good health, European Prospective Investigation into Cancer and Nutrition, PROGNOSTIC VALUE, Neopterina, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Lipid Metabolism Disorders::Dyslipidemias::Hyperlipidemias [Medical Subject Headings], 1107 Immunology, Biomarker (medicine), CORONARY-ARTERY-DISEASE, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Pteridines::Pterins::Biopterin::Neopterin [Medical Subject Headings], Life Sciences & Biomedicine, SERUM NEOPTERIN, medicine.medical_specialty, Clinical Sciences, Immunology, Clinical nutrition, Procesos Bioquímicos, ADVERSE CARDIAC EVENTS, 03 medical and health sciences, Clinical Research, Internal medicine, medicine, Journal Article, Nutrition, COLORECTAL-CANCER RISK, Cancer och onkologi, Proyectos de Investigación, Science & Technology, INTERFERON-GAMMA, business.industry, Research, 1103 Clinical Sciences, medicine.disease, Ageing, 030104 developmental biology, Blood pressure, Endocrinology, SYSTEM ACTIVATION, chemistry, Cardiovascular and Metabolic Diseases, Cancer and Oncology, Glycated hemoglobin, Hiperlipidemias, business, Hiperlipèmia
Abstract: BACKGROUND: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC).RESULTS: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p CONCLUSIONS: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.
Published: 2016

49. Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance

Author: Chong Yew Tan, Samuel Virtue, Steven Murfitt, Lee D. Robert, Yi Hui Phua, Martin Dale, Julian L. Griffin, Francisco Tinahones, Philipp E. Scherer, Antonio Vidal-Puig, [Yew Tan,C, Virtue,S, Dale,M, Vidal-Puig,A] University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, MDU MRC. Addenbrooke’s Hospital, Cambridge, UK. [Murfitt,S, Robert,LD, Phua,YH, Griffin,JL] University of Cambridge Department of Biochemistry, Cambridge, UK. [Tinahones,FJ] UGC Endocrinologia y Nutrición (IBIMA), Hospital Virgen de la Victoria. CIBER of Physiopathology, Obesity and Nutrition (CIBEROBN) Málaga, Spain. [Scherer,P] Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. [Vidal-Puig,A] Wellcome Trust Sanger Institute, Hinxton, Uk. [Robert,LD, Griffin,JL] Medical Research Council – Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, Uk., BB/H002731/1, Biotechnology and Biological Sciences Research Council, United Kingdom, BB/H013539/1, Biotechnology and Biological Sciences Research Council, United Kingdom, MC_G0802535, Medical Research Council, United Kingdom, MC_PC_13030, Medical Research Council, United Kingdom, MC_UP_A090_1006, Medical Research Council, United Kingdom, MC_UU_12012/2, Medical Research Council, United Kingdom, RG/12/13/29853, British Heart Foundation, United Kingdom, Griffin, Julian [0000-0003-1336-7744], Vidal-Puig, Antonio [0000-0003-4220-9577], and Apollo - University of Cambridge Repository
Subjects: Male, Tejido adiposo, Adenosine Deaminase, Fatty Acid Elongases, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::Adiponectin [Medical Subject Headings], Adipose Tissue, White, Obesidad, Mice, Obese, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance::Insulin Resistance [Medical Subject Headings], Grasa intra-abdominal, Severity of Illness Index, Gato, Grasa subcutánea, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, Acetyltransferases, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Essential [Medical Subject Headings], Organisms::Eukaryota::Animals [Medical Subject Headings], Animals, Obesity, Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White::Abdominal Fat::Intra-Abdominal Fat [Medical Subject Headings], Triglycerides, Chemicals and Drugs::Lipids::Glycerides::Triglycerides [Medical Subject Headings], Mice, Knockout, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Fatty Acids, food and beverages, Anatomy::Tissues::Connective Tissue::Adipose Tissue [Medical Subject Headings], Humanos, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Chemicals and Drugs::Inorganic Chemicals::Elements::Carbon [Medical Subject Headings], Ácidos grasos monoinsaturados, Adiposidad, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Body Composition::Body Fat Distribution::Adiposity [Medical Subject Headings], Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated [Medical Subject Headings], Female, lipids (amino acids, peptides, and proteins), Insulin Resistance, Adiponectina, Ácidos grasos, esenciales
Abstract: Journal Article; The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue. Yes
Published: 2015

50. Lipid-dependent regulation of the unfolded protein response

Author: Volmer, Romain, Ron, David, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Wellcome Trust-MRC Institute of Metabolic Science, Wellcome Trust, European Project: 277713,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,BETABAT(2011), Ron, David [0000-0002-3014-5636], Apollo - University of Cambridge Repository, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: Protein Folding, [SDV]Life Sciences [q-bio], Unfolded Protein Response, Animals, Eukaryota, Humans, Cell Biology, Endoplasmic Reticulum, Lipid Metabolism, Article, Molecular Chaperones, Signal Transduction
Abstract: International audience; Protein folding homeostasis in the lumen of the endoplasmic reticulum is defended by signal transduction pathways that are activated by an imbalance between unfolded proteins and chaperones (so called ER stress). Collectively referred to as the unfolded protein response (UPR) this homeostatic response is initiated by three known ER stress transducers: IRE1, PERK and ATF6. These ER-localised transmembrane (TM) proteins posses lumenal stress sensing domains and cytosolic effector domains that collectively activate a gene expression programme regulating the production of proteins involved in the processing and maturation of secreted proteins that enter the ER. However, beyond limiting unfolded protein stress in the ER the UPR has important connections to lipid metabolism that are the subject of this review.
Published: 2015

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