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1. In vivo identification of Drosophila rhodopsin interaction partners by biotin proximity labeling

Author: Nilofar Feizy, Sarah Franziska Leuchtenberg, Christine Steiner, Berit Würtz, Leo Fliegner, and Armin Huber
Subjects: Medicine, Science
Abstract: Abstract Proteins exert their function through protein–protein interactions. In Drosophila, G protein-coupled receptors like rhodopsin (Rh1) interact with a G protein to activate visual signal transduction and with arrestins to terminate activation. Also, membrane proteins like Rh1 engage in protein–protein interactions during folding within the endoplasmic reticulum, during their vesicular transport and upon removal from the cell surface and degradation. Here, we expressed a Rh1-TurboID fusion protein (Rh1::TbID) in Drosophila photoreceptors to identify in vivo Rh1 interaction partners by biotin proximity labeling. We show that Rh1::TbID forms a functional rhodopsin that mediates biotinylation of arrestin 2 in conditions where arrestin 2 interacts with rhodopsin. We also observed biotinylation of Rh1::TbID and native Rh1 as well as of most visual signal transduction proteins. These findings indicate that the signaling components in the rhabdomere approach rhodopsin closely, within a range of ca. 10 nm. Furthermore, we have detected proteins engaged in the maturation of rhodopsin and elements responsible for the trafficking of membrane proteins, resembling potential interaction partners of Rh1. Among these are chaperons of the endoplasmic reticulum, proteins involved in Clathrin-mediated endocytosis as well as previously unnoticed contributors to rhodopsin transportation, such as Rab32, Vap33, or PIP82.
Published: 2024
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2. Impact of an in-consult patient decision aid on treatment choices and outcomes of management for patients with an endoscopically resected malignant colorectal polyp: a study protocol for a non-randomised clinical phase II study

Author: Adrian Edwards, Karina Dahl Steffensen, Jan Lindebjerg, Helene Juul Würtz, and Hans Bjarke Rahr
Subjects: Medicine
Abstract: Introduction Management of an endoscopically resected malignant colorectal polyps can be challenging due to the risk of residual tumour and lymphatic spread. International studies have shown, that of those choosing surgical management instead of surveillance strategy, there are between 54% and 82% of bowel resections without evidence of residual tumour or lymphatic spread. As surgical management entails risks of complications and surveillance strategy entails risks of residual tumour or recurrence, a clinical dilemma arises when choosing a management strategy. Shared decision-making is a concept that can be used in preference-sensitive decision-making to facilitate patient involvement and empowerment to facilitate active patient participation in the decision-making process.Methods and analysis This study protocol describes our clinical multi-institutional, non-randomised, interventional phase II study at Danish surgical departments planned to commence in the second quarter of 2024. The aim of this study is to examine whether shared decision-making and using a patient decision aid in consultations affect patients’ choice of management, comparing with retrospective data. The secondary aim is to investigate patients’ experiences, perceived involvement, satisfaction, decision conflict and other outcomes using questionnaire feedback directly from the patients.Ethics and dissemination There are no conflicts of interest for principal or local investigators in any of the study sites. All results will be published at Danish and international meetings, and in English language scientific peer-reviewed journals. Our study underwent evaluation by the Regional Committees on Health Research Ethics for Southern Denmark (file number 20232000-47), concluding that formal approval was not required for this kind of research.Trial registration number NCT05776381.
Published: 2023
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3. Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation

Author: Courtney J Smith, Nasa Sinnott-Armstrong, Anna Cichońska, Heli Julkunen, Eric B Fauman, Peter Würtz, and Jonathan K Pritchard
Subjects: GWAS, genetic architecture, metabolites, Medicine, Science, Biology (General), QH301-705.5
Abstract: Pleiotropy and genetic correlation are widespread features in genome-wide association studies (GWAS), but they are often difficult to interpret at the molecular level. Here, we perform GWAS of 16 metabolites clustered at the intersection of amino acid catabolism, glycolysis, and ketone body metabolism in a subset of UK Biobank. We utilize the well-documented biochemistry jointly impacting these metabolites to analyze pleiotropic effects in the context of their pathways. Among the 213 lead GWAS hits, we find a strong enrichment for genes encoding pathway-relevant enzymes and transporters. We demonstrate that the effect directions of variants acting on biology between metabolite pairs often contrast with those of upstream or downstream variants as well as the polygenic background. Thus, we find that these outlier variants often reflect biology local to the traits. Finally, we explore the implications for interpreting disease GWAS, underscoring the potential of unifying biochemistry with dense metabolomics data to understand the molecular basis of pleiotropy in complex traits and diseases.
Published: 2022
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4. Cohort profile: the multigeneration Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort

Author: Thorarinn Gislason, Torben Sigsgaard, Vivi Schlünssen, Joachim Heinrich, Jesús Martínez-Moratalla, Øistein Svanes, Mathias Holm, Bertil Forsberg, Dan Norbäck, Rain Jogi, Kjell Torén, Deborah Jarvis, Magnus Ekström, Adrian Lowe, Caroline J Lodge, Michael Abramson, Shyamali Dharmage, Kathrine Pape, Cecilie Svanes, Gita Mishra, Caroline Lodge, Lyle Gurrin, Bruce Thompson, Eva Lindberg, Christer Janson, Simone Accordini, Ane Johannessen, Bryndis Benediktsdottir, Karl Franklin, Andrei Malinovschi, Anna Oudin, Francisco Gómez Real, José Luis Sánchez-Ramos, Lennart Bråbäck, Torgeir Storaas, Shanshan Xu, Julia Dratva, John Holloway, Jorunn Kirkeleit, Christine Cramer, Gro Tjalvin, Anne Mette Lund Würtz, Randi Jacobsen Bertelsen, Oskar Jõgi, Signe Timm, Francisco Javier Callejas, Raúl Godoy, Trude Duelien Skorge, Christine Drengenes, Nils Oskar Jõgi, Maryia Khomich, Toril Mørkve Knudsen, Ingrid Kuiper, Juan Pablo López-Cervantes, Marianne Lønnebotn, Shokouh Makvandi-Nejad, Antonio Pérez, Anders Røsland, Rajesh Shigdel, Svein Magne Skulstad, Kai Triebner, Hilde Vindenes, Jose Luis Sanchez, Jose Maldonado, David Martino, Jennifer Perret, Lucia Calciano, William Horsnell, and Susanne Krauss-Etchmann
Subjects: Medicine
Published: 2022
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5. DNA accessibility of chromatosomes quantified by automated image analysis of AFM data

Author: Martin Würtz, Dennis Aumiller, Lina Gundelwein, Philipp Jung, Christian Schütz, Kathrin Lehmann, Katalin Tóth, and Karl Rohr
Subjects: Medicine, Science
Abstract: Abstract DNA compaction and accessibility in eukaryotes are governed by nucleosomes and orchestrated through interactions between DNA and DNA-binding proteins. Using QuantAFM, a method for automated image analysis of atomic force microscopy (AFM) data, we performed a detailed statistical analysis of structural properties of mono-nucleosomes. QuantAFM allows fast analysis of AFM images, including image preprocessing, object segmentation, and quantification of different structural parameters to assess DNA accessibility of nucleosomes. A comparison of nucleosomes reconstituted with and without linker histone H1 quantified H1’s already described ability of compacting the nucleosome. We further employed nucleosomes bearing two charge-modifying mutations at position R81 and R88 in histone H2A (H2A R81E/R88E) to characterize DNA accessibility under destabilizing conditions. Upon H2A mutation, even in presence of H1, the DNA opening angle at the entry/exit site was increased and the DNA wrapping length around the histone core was reduced. Interestingly, a distinct opening of the less bendable DNA side was observed upon H2A mutation, indicating an enhancement of the intrinsic asymmetry of the Widom-601 nucleosomes. This study validates AFM as a technique to investigate structural parameters of nucleosomes and highlights how the DNA sequence, together with nucleosome modifications, can influence the DNA accessibility.
Published: 2019
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6. Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

Author: Heli Julkunen, Anna Cichońska, P Eline Slagboom, Peter Würtz, and Nightingale Health UK Biobank Initiative
Subjects: biomarkers, pneumonia, covid-19, Medicine, Science, Biology (General), QH301-705.5
Abstract: Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids, and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.
Published: 2021
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7. Lettuce (Lactuca sativa, variety Salanova) production in decoupled aquaponic systems: Same yield and similar quality as in conventional hydroponic systems but drastically reduced greenhouse gas emissions by saving inorganic fertilizer.

Author: Hendrik Monsees, Johanna Suhl, Maurice Paul, Werner Kloas, Dennis Dannehl, and Sven Würtz
Subjects: Medicine, Science
Abstract: Decoupled aquaponic systems have the potential to become one of the most effective sustainable production systems for the combined production of animal protein and plant crops. Here, recirculating aquaculture systems for fish production are combined with hydroponics for soilless plant production thereby recycling dissolved nutrients derived from metabolism of the fish. The aim of the present study was to characterize hydroponic lettuce production using conventional nutrient solution in comparison with decoupled aquaponics using the nutrient rich fish water as basis for the nutrient solution being supplemented by missing nutrients. In addition, one aquaponic treatment became disinfected in order to assess any occurring advantage of the aquaponics derived fish water. For evaluation the temperature, electrical conductivity, pH, and the mineral composition of the nutrient solution, as well as colony forming units in the fish water were monitored. Additionally, plant growth (fresh and dry weight, number and area of leaves) and quality parameters of lettuce leaves (nitrate, mineral content, phenolic compounds) were examined. Carbon sources and microorganisms derived from fish water seem to have neither beneficial nor detrimental effects on plant growth in this study. Except for some differences in the mineral content of the lettuce leaves, all other quality parameters were not significantly different. The use of aquaponic fish water saved 62.8% mineral fertilizer and fully substituted the required water for the nutrient solution in comparison to the control. Additionally, the reduced fertilizer demand using decoupled aquaponics can contribute to reduce greenhouse gas emissions of an annual lettuce production site per ha by 72% due to saving the energy for fertilizer production. This study clearly demonstrates the huge potential of the innovative approach of decoupled aquaponics to foster the transformation of our conventional agriculture towards sustainable production systems saving resources and minimizing emissions.
Published: 2019
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8. Elevated serum alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality.

Author: Scott C Ritchie, Johannes Kettunen, Marta Brozynska, Artika P Nath, Aki S Havulinna, Satu Männistö, Markus Perola, Veikko Salomaa, Mika Ala-Korpela, Gad Abraham, Peter Würtz, and Michael Inouye
Subjects: Medicine, Science
Abstract: BackgroundGlycA is a nuclear magnetic resonance (NMR) spectroscopy biomarker that predicts risk of disease from myriad causes. It is heterogeneous; arising from five circulating glycoproteins with dynamic concentrations: alpha-1 antitrypsin (AAT), alpha-1-acid glycoprotein (AGP), haptoglobin (HP), transferrin (TF), and alpha-1-antichymotrypsin (AACT). The contributions of each glycoprotein to the disease and mortality risks predicted by GlycA remain unknown.MethodsWe trained imputation models for AAT, AGP, HP, and TF from NMR metabolite measurements in 626 adults from a population cohort with matched NMR and immunoassay data. Levels of AAT, AGP, and HP were estimated in 11,861 adults from two population cohorts with eight years of follow-up, then each biomarker was tested for association with all common endpoints. Whole blood gene expression data was used to identify cellular processes associated with elevated AAT.ResultsAccurate imputation models were obtained for AAT, AGP, and HP but not for TF. While AGP had the strongest correlation with GlycA, our analysis revealed variation in imputed AAT levels was the most predictive of morbidity and mortality for the widest range of diseases over the eight year follow-up period, including heart failure (meta-analysis hazard ratio = 1.60 per standard deviation increase of AAT, P-value = 1×10-10), influenza and pneumonia (HR = 1.37, P = 6×10-10), and liver diseases (HR = 1.81, P = 1×10-6). Transcriptional analyses revealed association of elevated AAT with diverse inflammatory immune pathways.ConclusionsThis study clarifies the molecular underpinnings of the GlycA biomarker's associated disease risk, and indicates a previously unrecognised association between elevated AAT and severe disease onset and mortality.
Published: 2019
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9. Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease.

Author: Claus Uhrenholt Christensen, Emilie Glavind, Karen Louise Thomsen, Yong Ook Kim, Sara Heebøll, Detlef Schuppan, Stephen Hamilton-Dutoit, Christian Würtz Heegaard, and Henning Grønbæk
Subjects: Medicine, Science
Abstract: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model.Rats were fed a high-fat, high-cholesterol (HFHC) diet for four weeks resulting in moderately severe NASH. Animals were treated with intravenous NPC2 or placebo twice weekly for either the last two weeks or the entire four weeks. End-points were liver/body- and spleen/body weight ratios, histopathological NASH scores, fibrosis, serum liver enzymes, cholesterol, lipoproteins, cytokines, and quantitative polymerase chain reaction derived hepatic gene expression related to cholesterol metabolism, inflammation, and fibrosis.HFHC rats developed hepatomegaly, non-fibrotic NASH histopathology, elevated liver enzymes, serum cholesterol, and pro-inflammatory cytokines. Their sterol regulatory element binding factor 2 (SREBF2) and low-density lipoprotein receptor (LDL-R) mRNAs were down-regulated compared with rats on standard chow. NPC2 did not improve liver weight, histopathology, levels of serum liver enzymes or pro-inflammatory tumor necrosis factor-α (TNFα), Interleukin (IL)-6, or IL-1β in HFHC rats. Two weeks of NPC2 treatment lowered hepatic TNFα and COL1A1 mRNA expression. However, this effect was ultimately reversed following additional two weeks of treatment. Four weeks NPC2 treatment of rats raised ATP-binding cassette A1 (ABCA1) and low-density lipoprotein receptor (LDLR) mRNAs in the liver, concurrent with a strong tendency towards higher serum high-density lipoprotein (HDL). Furthermore, the peroxisome proliferator activated receptor-ɣ (PPARG) gene expression was reduced.NPC2 proved inefficient at modifying robust hepatic NASH end-points in a HFHC NASH model. Nonetheless, our data suggest that hepatic ABCA1 expression and reverse cholesterol transport were upregulated by NPC2 treatment, thus presenting putative therapeutic effects in diseases associated with deregulated lipid metabolism.
Published: 2018
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10. The population attributable fraction of occupational COPD among Danish women

Author: Else Würtz, Vivi Schlünssen, Tine Malling, Jens Georg Hansen, and Øyvind Omland
Subjects: Medicine
Published: 2017
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11. Coronary artery disease-associated genetic variants and biomarkers of inflammation.

Author: Morten Krogh Christiansen, Sanne Bøjet Larsen, Mette Nyegaard, Søs Neergaard-Petersen, Ramzi Ajjan, Morten Würtz, Erik Lerkevang Grove, Anne-Mette Hvas, Henrik Kjærulf Jensen, and Steen Dalby Kristensen
Subjects: Medicine, Science
Abstract: Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD-associated SNPs and five CAD-related inflammatory biomarkers.We genotyped 45 CAD-associated SNPs in 701 stable CAD patients in whom levels of high-sensitivity C-reactive protein (hsRCP), interleukin-6, calprotectin, fibrinogen and complement component 3 levels had previously been measured. A genetic risk score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers.The minor allele (G) (CAD risk allele) of rs2075650 (TOMM40/APOE) was associated with lower levels of high-sensitivity C-reactive protein (effect per risk allele: -0.37 mg/l [95%CI -0.56 to -0.18 mg/l]). The inflammatory markers tested showed no association with the remaining 44 SNPs or with the genetic risk score.In stable CAD patients, the risk allele of a common CAD-associated marker at the TOMM40/APOE locus was associated with lower hsCRP levels. No other genetic variants or the combined effect of all variants were associated with the five inflammatory biomarkers.
Published: 2017
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12. Social and Psychological Predictors of Initial Cigarette Smoking Experience

Author: Walieh Menati MSc, Milad Nazarzadeh MSc, Zeinab Bidel MSc, Morten Würtz MD, Rostam Menati MSc, Rohollah Hemati IM, CD, Maryam Yaghoubi BS, Elham Zareimanesh BS, Mohammad Sabour Mohammadi BS, Farzad Akhlaghi Ardekani BS, Jafar Tazval MSc, and Ali Delpisheh PhD
Subjects: Medicine
Abstract: Knowledge about social and psychological risk factors for initial cigarette smoking experience (ICSE) is sparse. The present study aimed to estimate the prevalence of ICSE and to examine the psychological and social factors related to ICSE. In a cross-sectional survey, 1,511 male college students were recruited using multistage sampling techniques from four universities located within the city of Ilam, Iran. Self-administered multiple-choice questionnaires were distributed to students from March to June 2013. Risk factors for ICSE were evaluated using logistic regression models. Participants were 22.3 ± 2.4 years of age. ICSE prevalence was 30.6%. In multivariable adjusted analysis, risk taking behavior (odds ratio [OR] = 1.61; 95% confidence interval [CI] = 1.11-2.33), perceived peer smoking prevalence (OR = 2.48; 95% CI = 1.03-5.97), positive thoughts about smoking (OR = 1.06; 95% CI = 1.02-1.10), high self-efficacy ( OR = 0.95, 95% CI [0.93, 0.98]), presence in smokers’ gathering (OR = 4.45; 95% CI = 2.88-6.81), comity of smokers (OR = 2.56; 95% CI = 1.66, 3.92), very hard access to cigarettes (OR = 2.20; 95% CI = 1.16-4.16), close friends’ medium reaction toward smoking (OR = 1.38; 95% CI = 1.02-1.88), and sporting activity (OR = 0.74; 95% CI = 0.56-0.98) were significantly associated with ICSE. This study identified that a combination of psychological and social variables account for up to 78% of the probability of ICSE. The most important protective factor against ICSE was physical activity, whereas the most important risk factor for ICSE was frequent gathering in the presence of smokers.
Published: 2016
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13. Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease.

Author: Sanne Bøjet Larsen, Erik Lerkevang Grove, Søs Neergaard-Petersen, Morten Würtz, Anne-Mette Hvas, and Steen Dalby Kristensen
Subjects: Medicine, Science
Abstract: Aspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported.To investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients.We performed a cross-sectional study including 900 stable, high-risk CAD patients. Among these, 795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170 (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. The antiplatelet effect of aspirin was assessed by measurement of platelet aggregation employing 1) multiple electrode aggregometry (MEA, Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay. Compliance was assessed by measurement of serum thromboxane B2.Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased AA-induced MEA platelet aggregation in citrate and hirudin anticoagulated blood (p-values ≤ 0.045). Similar results were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent determinants of increased platelet aggregation (p-values ≤ 0.038). Compliance was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml).Platelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased platelet aggregation, indicating that these characteristics may be key factors in reduced antiplatelet effect of aspirin in stable CAD patients.
Published: 2015
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14. Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

Author: Peter Würtz, Qin Wang, Antti J Kangas, Rebecca C Richmond, Joni Skarp, Mika Tiainen, Tuulia Tynkkynen, Pasi Soininen, Aki S Havulinna, Marika Kaakinen, Jorma S Viikari, Markku J Savolainen, Mika Kähönen, Terho Lehtimäki, Satu Männistö, Stefan Blankenberg, Tanja Zeller, Jaana Laitinen, Anneli Pouta, Pekka Mäntyselkä, Mauno Vanhala, Paul Elliott, Kirsi H Pietiläinen, Samuli Ripatti, Veikko Salomaa, Olli T Raitakari, Marjo-Riitta Järvelin, George Davey Smith, and Mika Ala-Korpela
Subjects: Medicine
Abstract: BackgroundIncreased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood.Methods and findingsWe used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/m(2)). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (pConclusionsMendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.
Published: 2014
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15. Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.

Author: Krista Fischer, Johannes Kettunen, Peter Würtz, Toomas Haller, Aki S Havulinna, Antti J Kangas, Pasi Soininen, Tõnu Esko, Mari-Liis Tammesoo, Reedik Mägi, Steven Smit, Aarno Palotie, Samuli Ripatti, Veikko Salomaa, Mika Ala-Korpela, Markus Perola, and Andres Metspalu
Subjects: Medicine
Abstract: BackgroundEarly identification of ambulatory persons at high short-term risk of death could benefit targeted prevention. To identify biomarkers for all-cause mortality and enhance risk prediction, we conducted high-throughput profiling of blood specimens in two large population-based cohorts.Methods and findings106 candidate biomarkers were quantified by nuclear magnetic resonance spectroscopy of non-fasting plasma samples from a random subset of the Estonian Biobank (n = 9,842; age range 18-103 y; 508 deaths during a median of 5.4 y of follow-up). Biomarkers for all-cause mortality were examined using stepwise proportional hazards models. Significant biomarkers were validated and incremental predictive utility assessed in a population-based cohort from Finland (n = 7,503; 176 deaths during 5 y of follow-up). Four circulating biomarkers predicted the risk of all-cause mortality among participants from the Estonian Biobank after adjusting for conventional risk factors: alpha-1-acid glycoprotein (hazard ratio [HR] 1.67 per 1-standard deviation increment, 95% CI 1.53-1.82, p = 5×10⁻³¹), albumin (HR 0.70, 95% CI 0.65-0.76, p = 2×10⁻¹⁸), very-low-density lipoprotein particle size (HR 0.69, 95% CI 0.62-0.77, p = 3×10⁻¹²), and citrate (HR 1.33, 95% CI 1.21-1.45, p = 5×10⁻¹⁰). All four biomarkers were predictive of cardiovascular mortality, as well as death from cancer and other nonvascular diseases. One in five participants in the Estonian Biobank cohort with a biomarker summary score within the highest percentile died during the first year of follow-up, indicating prominent systemic reflections of frailty. The biomarker associations all replicated in the Finnish validation cohort. Including the four biomarkers in a risk prediction score improved risk assessment for 5-y mortality (increase in C-statistics 0.031, p = 0.01; continuous reclassification improvement 26.3%, p = 0.001).ConclusionsBiomarker associations with cardiovascular, nonvascular, and cancer mortality suggest novel systemic connectivities across seemingly disparate morbidities. The biomarker profiling improved prediction of the short-term risk of death from all causes above established risk factors. Further investigations are needed to clarify the biological mechanisms and the utility of these biomarkers for guiding screening and prevention.
Published: 2014
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16. Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.

Author: Morten Würtz, Peter H Nissen, Erik Lerkevang Grove, Steen Dalby Kristensen, and Anne-Mette Hvas
Subjects: Medicine, Science
Abstract: Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan). Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen) and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1) gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.A common genetic variant in PEAR1 (rs12041331) reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.ClinicalTrials.gov NCT01383304.
Published: 2014
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17. Classification and visualization based on derived image features: application to genetic syndromes.

Author: Brunilda Balliu, Rolf P Würtz, Bernhard Horsthemke, Dagmar Wieczorek, and Stefan Böhringer
Subjects: Medicine, Science
Abstract: Data transformations prior to analysis may be beneficial in classification tasks. In this article we investigate a set of such transformations on 2D graph-data derived from facial images and their effect on classification accuracy in a high-dimensional setting. These transformations are low-variance in the sense that each involves only a fixed small number of input features. We show that classification accuracy can be improved when penalized regression techniques are employed, as compared to a principal component analysis (PCA) pre-processing step. In our data example classification accuracy improves from 47% to 62% when switching from PCA to penalized regression. A second goal is to visualize the resulting classifiers. We develop importance plots highlighting the influence of coordinates in the original 2D space. Features used for classification are mapped to coordinates in the original images and combined into an importance measure for each pixel. These plots assist in assessing plausibility of classifiers, interpretation of classifiers, and determination of the relative importance of different features.
Published: 2014
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18. Protein replacement therapy partially corrects the cholesterol-storage phenotype in a mouse model of Niemann-Pick type C2 disease.

Author: Gitte Krogh Nielsen, Frederik Dagnaes-Hansen, Ida Elisabeth Holm, Steve Meaney, Derek Symula, Niels Trolle Andersen, and Christian Würtz Heegaard
Subjects: Medicine, Science
Abstract: Niemann-Pick type C2 (NPC2) disease is a fatal autosomal recessive neurovisceral degenerative disorder characterized by late endosomal-lysosomal sequestration of low-density lipoprotein derived cholesterol. The breach in intracellular cholesterol homeostasis is caused by deficiency of functional NPC2, a soluble sterol binding protein targeted to the lysosomes by binding the mannose-6-phosphate receptor. As currently there is no effective treatment for the disorder, we have investigated the efficacy of NPC2 replacement therapy in a murine gene-trap model of NPC2-disease generated on the 129P2/OlaHsd genetic background. NPC2 was purified from bovine milk and its functional competence assured in NPC2-deficient fibroblasts using the specific cholesterol fluorescent probe filipin. For evaluation of phenotype correction in vivo, three-week-old NPC2(-/-) mice received two weekly intravenous injections of 5 mg/kg NPC2 until trial termination 66 days later. Whereas the saline treated NPC2(-/-) mice exhibited massive visceral cholesterol storage as compared to their wild-type littermates, administration of NPC2 caused a marked reduction in cholesterol build up. The histological findings, indicating an amelioration of the disease pathology in liver, spleen, and lungs, corroborated the biochemical results. Little or no difference in the overall cholesterol levels was observed in the kidneys, blood, cerebral cortex and hippocampus when comparing NPC2(-/-) and wild type mice. However, cerebellum cholesterol was increased about two fold in NPC2(-/-) mice compared with wild-type littermates. Weight gain performance was slightly improved as a result of the NPC2 treatment but significant motor coordination deficits were still observed. Accordingly, ultrastructural cerebellar abnormalities were detected in both saline treated and NPC2 treated NPC2(-/-) animals 87 days post partum. Our data indicate that protein replacement may be a beneficial therapeutic approach in the treatment of the visceral manifestations in NPC2 disease and further suggest that neurodegeneration is not secondary to visceral dysfunction.
Published: 2011
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19. A differential network approach to exploring differences between biological states: an application to prediabetes.

Author: Beatriz Valcárcel, Peter Würtz, Nafisa-Katrin Seich al Basatena, Taru Tukiainen, Antti J Kangas, Pasi Soininen, Marjo-Riitta Järvelin, Mika Ala-Korpela, Timothy M Ebbels, and Maria de Iorio
Subjects: Medicine, Science
Abstract: Variations in the pattern of molecular associations are observed during disease development. The comprehensive analysis of molecular association patterns and their changes in relation to different physiological conditions can yield insight into the biological basis of disease-specific phenotype variation.Here, we introduce a formal statistical method for the differential analysis of molecular associations via network representation. We illustrate our approach with extensive data on lipoprotein subclasses measured by NMR spectroscopy in 4,406 individuals with normal fasting glucose, and 531 subjects with impaired fasting glucose (prediabetes). We estimate the pair-wise association between measures using shrinkage estimates of partial correlations and build the differential network based on this measure of association. We explore the topological properties of the inferred network to gain insight into important metabolic differences between individuals with normal fasting glucose and prediabetes.Differential networks provide new insights characterizing differences in biological states. Based on conventional statistical methods, few differences in concentration levels of lipoprotein subclasses were found between individuals with normal fasting glucose and individuals with prediabetes. By performing the differential analysis of networks, several characteristic changes in lipoprotein metabolism known to be related to diabetic dyslipidemias were identified. The results demonstrate the applicability of the new approach to identify key molecular changes inaccessible to standard approaches.
Published: 2011
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20. Biomarker Profiling by Nuclear Magnetic Resonance Spectroscopy for the Prediction of All-Cause Mortality: An Observational Study of 17,345 Persons

Author: Fischer, Krista, Kettunen, Johannes, Würtz, Peter, Haller, Toomas, Havulinna, Aki S., Kangas, Antti J., Soininen, Pasi, Esko, Tõnu, Tammesoo, Mari-Liis, Mägi, Reedik, Smit, Steven, Palotie, Aarno, Ripatti, Samuli, Salomaa, Veikko, Ala-Korpela, Mika, Perola, Markus, and Metspalu, Andres
Subjects: Biology, Biochemistry, Blood chemistry, Metabolism, Biotechnology, Medicine, Diagnostic medicine, Clinical laboratory sciences, Clinical chemistry, Epidemiology, Biomarker epidemiology, Epidemiology of aging, Molecular epidemiology, Public health, Preventive medicine
Abstract: Background: Early identification of ambulatory persons at high short-term risk of death could benefit targeted prevention. To identify biomarkers for all-cause mortality and enhance risk prediction, we conducted high-throughput profiling of blood specimens in two large population-based cohorts. Methods and Findings: 106 candidate biomarkers were quantified by nuclear magnetic resonance spectroscopy of non-fasting plasma samples from a random subset of the Estonian Biobank (n = 9,842; age range 18–103 y; 508 deaths during a median of 5.4 y of follow-up). Biomarkers for all-cause mortality were examined using stepwise proportional hazards models. Significant biomarkers were validated and incremental predictive utility assessed in a population-based cohort from Finland (n = 7,503; 176 deaths during 5 y of follow-up). Four circulating biomarkers predicted the risk of all-cause mortality among participants from the Estonian Biobank after adjusting for conventional risk factors: alpha-1-acid glycoprotein (hazard ratio [HR] 1.67 per 1–standard deviation increment, 95% CI 1.53–1.82, p = 5×10−31), albumin (HR 0.70, 95% CI 0.65–0.76, p = 2×10−18), very-low-density lipoprotein particle size (HR 0.69, 95% CI 0.62–0.77, p = 3×10−12), and citrate (HR 1.33, 95% CI 1.21–1.45, p = 5×10−10). All four biomarkers were predictive of cardiovascular mortality, as well as death from cancer and other nonvascular diseases. One in five participants in the Estonian Biobank cohort with a biomarker summary score within the highest percentile died during the first year of follow-up, indicating prominent systemic reflections of frailty. The biomarker associations all replicated in the Finnish validation cohort. Including the four biomarkers in a risk prediction score improved risk assessment for 5-y mortality (increase in C-statistics 0.031, p = 0.01; continuous reclassification improvement 26.3%, p = 0.001). Conclusions: Biomarker associations with cardiovascular, nonvascular, and cancer mortality suggest novel systemic connectivities across seemingly disparate morbidities. The biomarker profiling improved prediction of the short-term risk of death from all causes above established risk factors. Further investigations are needed to clarify the biological mechanisms and the utility of these biomarkers for guiding screening and prevention. Please see later in the article for the Editors' Summary
Published: 2014
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21. 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, 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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, 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P., Esko, T., Fall, T., Chen, H., Robertson, N., Rybin, D., Chines, PS., Song, K., An, P., Marullo, L., Jansen, H., Oldehinkel, AJ., North, KE., Forouhi, NG., Edkins, S., Varga, TV., Oksa, H., Antonella, M., Kong, A., Herder, C., Antti, J., Miljkovic, I., Atalay, M., Kiess, W., James, AL., Smit, JH., Campbell, S., Fowkes, GR., Basart, HV., Rathmann, W., Maerz, W., Province, MA., Watanabe, RM., de Geus EJ., Penninx, BW., Oostra, B., Toenjes, A., Peyser, PA., Körner, A., Keinanen-Kiukaanniemi, SM., Saaristo, TE., Boomsma, D., Cucca, F., Balkau, B., Froguel, P., Jarvelin, MR., Bouatia-Naji, N., Ahmadi, KR., Ainali, C., Barrett, A., Bataille, V., Bell, JT., Buil, A., Dermitzakis, ET., Dimas, AS., Durbin, R., Glass, D., Hassanali, N., Hedman£££Åsa K£££ ÅK., Ingle, C., Keildson, S., Knowles, D., Krestyaninova, M., Lowe, CE., Meduri, E., di Meglio, P., Min, JL., Montgomery, SB., Nestle, FO., Nica, AC., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, SY., Small, KS., 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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, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, King‘s College London, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, 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), 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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(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 Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [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 ), University of California [Irvine] (UCI), German Research Center for Environmental Health, University of Bonn, Czech Academy of Sciences [Prague] (ASCR), Yale University School of Medicine, University of Oxford [Oxford], German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Laval University, Laval University [Québec], Turku University Hospital, Lausanne university hospital, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de biologie de Lille - IBL (IBLI), 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, 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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

22. Genetic studies of body mass index yield new insights for obesity biology

Author: Locke, Adam E, Kahali, Bratati, Croteau-Chonka, Damien C, Doney, Alex S F, He, Bing, Heikkilä, Outi, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Eklund, Niina, Saraheimo, Markku, Sarti, Cinzia, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Estrada, Karol, Wadén, Johan, Gill, Geoffrey V, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Eury, Elodie, Ladenvall, Claes, Alhenc-Gelas, François, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Folkersen, Lasse, Möllsten, Anna, Cimponeriu, Dan, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Fraser, Ross M, Colhoun, Helen M, Panduru, Nicolae Mircea, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Garcia, Melissa E, 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, Geller, Frank, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Giedraitis, Vilmantas, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Y, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Gigante, Bruna, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Esko, Tonu, Go, Alan S, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Golay, Alain, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Goodall, Alison H, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Gordon, Scott D, 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, Gorski, Mathias, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doring, Angela, Elliott, Paul, Grabe, Hans-Jörgen, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Khaw, Kay-Tee, Kim, Eric, Grammer, Tanja B, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J F, Mach, François, McArdle, Wendy L, Gräßler, Jürgen, Meisinger, Christa, Mitchell, Braxton D, Muller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Grönberg, Henrik, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Ridker, Paul M, Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Fall, Tove, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, 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Harris, T, Hattersley, A, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Homuth, G, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Illig, T, Jacobs, K, Jarvelin, M, Jockel, K, Johansen, B, Jousilahti, P, Jukema, J, Jula, A, Kaprio, J, Kastelein, J, Keinanen-Kiukaanniemi, S, Kiemeney, L, Knekt, P, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Marchand, L, Lehtimaki, T, Lyssenko, V, Mannisto, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Moll, F, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Madden, P, Pasterkamp, G, Peden, J, Peters, A, Postma, D, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Rioux, J, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schunkert, H, Schwarz, P, Sever, P, Shuldiner, A, Sinisalo, J, Stolk, R, Strauch, K, Tonjes, A, Tregouet, D, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Volker, U, Waeber, G, Willemsen, G, Witteman, J, Zillikens, M, Adair, L, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bornstein, S, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hui, J, Hunter, D, Hveem, K, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, Marz, W, Melbye, M, Metspalu, A, Moebus, S, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Perusse, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sattar, N, Schadt, E, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Walker, M, Wallaschofski, H, Wareham, N, Watkins, H, Weir, D, Wichmann, H, Wilson, J, Zanen, P, Borecki, I, Deloukas, P, Fox, C, Heid, I, O'Connell, J, Strachan, D, Stefansson, K, van Duijn, C, Abecasis, G, Franke, L, Frayling, T, Mccarthy, M, Visscher, P, Scherag, A, Willer, C, Boehnke, M, Mohlke, K, Lindgren, C, Beckmann, J, Barroso, I, North, K, Ingelsson, E, Hirschhorn, J, Loos, R, Speliotes, E, Thompson, J, Goldstein, B, Konig, I, Cazier, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikainen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Claudi-Boehm, S, Cox, D, 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, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schafer, A, Sivananthan, M, Song, C, Stewart, A, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Tsun-Po, Y, Basart, H, Brambilla, P, Cambien, F, Cupples, A, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kahonen, M, Kee, F, Kim, H, Klopp, N, Kuulasmaa, K, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Wallentin, L, Zimmermann, M, Nieminen, M, Sandhu, M, Pastinen, T, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Roberts, R, Pattaro, C, Kottgen, A, Garnaas, M, Boger, C, Fuchsberger, C, Olden, M, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Liu, C, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Lohman, K, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, Hu, F, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Doring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Ellinghaus, D, Nothlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, 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S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Makinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkila, O, Hietala, K, Kyto, J, Lahermo, P, Lehto, M, Osterholm, A, Parkkonen, M, Pitkaniemi, J, Rosengard-Barlund, M, Saraheimo, M, Sarti, C, Soderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Waden, 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, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Mollsten, 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, Freitag, D, Gurdasani, D, Heikkila, K, Johnson, T, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Teslovich, T, Van den Herik, E, Volcik, K, Wu, Y, Asiki, G, Been, L, Burnett, M, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Khaw, K, Kim, E, Komulainen, P, Lin, S, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Young, E, Bennett, F, Boomsma, D, Burnier, M, Feranil, A, Freimer, N, Hsiung, C, Kesaniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Meneton, P, Moilanen, L, 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, Sober, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjogren, 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, Brown, M, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Staessen, J, 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, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, 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, Wurtz, P, Ong, R, Dorr, M, 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, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, Ormel, J, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Rasmussen-Torvik, L, Lecoeur, C, Johnson, P, Sennblad, B, Salo, P, Timpson, N, Evans, D, St Pourcain, B, Bielak, L, Horikoshi, M, Navarro, P, Raychaudhuri, S, Chen, H, Rybin, D, Willems, S, Song, K, An, P, Marullo, L, Jansen, H, Pankow, J, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Small, K, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Penninx, B, Toenjes, A, Peyser, P, Korner, A, Dupuis, J, Cucca, F, Balkau, B, Bouatia-Naji, N, Purcell, S, Musunuru, K, Ardissino, D, Mannucci, P, Anand, S, Engert, J, Morgan, T, Spertus, J, Stoll, M, Girelli, D, Mckeown, P, Patterson, C, Merlini, P, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Subirana, I, Sala, J, Ramos, R, Williams, G, Nathan, D, Macrae, C, Berglund, G, Asselta, R, Duga, S, Spreafico, M, Daly, M, Nemesh, J, Korn, J, Surti, A, Gianniny, L, Parkin, M, Burtt, N, Gabriel, S, Wright, B, Ball, S, Schunkert, I, Linsel-Nitschke, P, Lieb, W, Fischer, M, Grosshennig, A, Preuss, M, Scholz, M, Chen, Z, Wilensky, R, Matthai, W, Qasim, A, Hakonarson, H, Devaney, J, Pichard, A, Kent, K, Satler, L, Lindsay, J, Waksman, R, Knouff, C, Scheffold, T, Berger, K, Huge, A, Martinelli, N, Olivieri, O, Corrocher, R, Xie, C, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, 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, Yang, T, Higashio, J, Williams, R, Nato, A, Ambite, J, Deelman, E, Manolio, T, 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, Bush, W, Mitchell, S, Goodloe, R, Wilson, S, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Spencer, K, Pendergrass, S, Le Marchand, L, Park, L, Tiirikainen, M, Kolonel, L, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Anderson, G, Carlson, C, Prentice, R, Lacroix, A, Wu, C, Carty, C, Rosse, S, Young, A, Kocarnik, J, Lin, Y, Jackson, R, Duggan, D, 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, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hankinson, S, Hass, M, Janssens, A, Karasik, D, Keyzer, J, Kiel, D, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Streeten, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Koller, D, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Couper, D, Easton, D, Foroud, T, Kilpelainen, T, Li, S, Murray, S, Ness, A, Northstone, K, Peacock, M, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segre, A, Sovio, U, Srinivasan, S, Tammesoo, M, van Meurs, J, Young, L, Bierut, L, Econs, M, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Berndt, Sonja I, Justice, Anne E, Hyppönen, Elina Tuulikki, Epidemiology and Data Science, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Male, LOCI, Genome-wide association study, Continental Population Groups/genetics, VARIANTS, Body Mass Index, Insulin Secretion, Insulin, Age Factor, Adiposity, ddc:616, Adipogenesis, Genetic Predisposition to Disease/genetics, Synapse, 3. Good health, Continental Population Group, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], GENOME-WIDE ASSOCIATIONPROVIDES INSIGHTSGLYCEMIC TRAITSLOCIMETAANALYSISVARIANTSINDIVIDUALSHIPPOCAMPALARCHITECTURETOPIRAMATE, ddc:500, Adipogenesis/genetics, Single Nucleotide/genetics, Age Factors, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Glutamic Acid, Humans, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses, Genome-Wide Association Study, Multidisciplinary, genetics [Adiposity], Human, Socio-culturale, genetics [Energy Metabolism], ta3111, genetic, body mass index, obesity, SDG 3 - Good Health and Well-being, GLYCEMIC TRAITS, genetics [Continental Population Groups], Genetic variability, Polymorphism, GENOME-WIDE ASSOCIATION, genetics [Adipogenesis], METAANALYSIS, Genetic association, Adipogenesi, genetics [Quantitative Trait Loci], ta1184, metabolism [Glutamic Acid], ta1182, PATHWAYS, metabolism [Synapses], ta3121, medicine.disease, metabolism [Insulin], Adiposity/genetics, Clinical Medicine, Quantitative Trait Loci/genetics, Body mass index, HUMAN HEIGHT, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Synapses/metabolism, Medizin, Obesity/genetics, Bioinformatics, genetic basis, Obesity/metabolism, genetics [Obesity], body mass index (BMI), genetics [Genetic Predisposition to Disease], ethnology [Europe], 2. Zero hunger, Genetics, ARCHITECTURE, Genetics of obesity, Medicine (all), Single Nucleotide, Polymorphism, Single Nucleotide/genetics, Insulin/metabolism/secretion, Glutamic Acid/metabolism, genetics [Polymorphism, Single Nucleotide], EXPRESSION, Insulin/metabolism, PROVIDES INSIGHTS, genetics [Racial Groups], Biology, Obesity/genetics/metabolism, Europe/ethnology, metabolism [Obesity], Mendelian randomization, medicine, Energy Metabolism/genetics, body mass, genetic analysis, obesity, Klinisk medicin
Abstract: Item does not contain fulltext Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Published: 2015

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22 results on '"Würtz P"'

1. In vivo identification of Drosophila rhodopsin interaction partners by biotin proximity labeling

2. Impact of an in-consult patient decision aid on treatment choices and outcomes of management for patients with an endoscopically resected malignant colorectal polyp: a study protocol for a non-randomised clinical phase II study

3. Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation

4. Cohort profile: the multigeneration Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort

5. DNA accessibility of chromatosomes quantified by automated image analysis of AFM data

6. Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

7. Lettuce (Lactuca sativa, variety Salanova) production in decoupled aquaponic systems: Same yield and similar quality as in conventional hydroponic systems but drastically reduced greenhouse gas emissions by saving inorganic fertilizer.

8. Elevated serum alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality.

9. Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease.

10. The population attributable fraction of occupational COPD among Danish women

11. Coronary artery disease-associated genetic variants and biomarkers of inflammation.

12. Social and Psychological Predictors of Initial Cigarette Smoking Experience

13. Determinants of reduced antiplatelet effect of aspirin in patients with stable coronary artery disease.

14. Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

15. Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.

16. Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.

17. Classification and visualization based on derived image features: application to genetic syndromes.

18. Protein replacement therapy partially corrects the cholesterol-storage phenotype in a mouse model of Niemann-Pick type C2 disease.

19. A differential network approach to exploring differences between biological states: an application to prediabetes.

20. Biomarker Profiling by Nuclear Magnetic Resonance Spectroscopy for the Prediction of All-Cause Mortality: An Observational Study of 17,345 Persons

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

22. Genetic studies of body mass index yield new insights for obesity biology

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22 results on '"Würtz P"'

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