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201. Genetic analysis of over one million people identifies 535 novel loci for blood pressure

Author: Lorenz Risch, Anne-Claire Vergnaud, Nguyen Quang Tri, Rona J. Strawbridge, Alan F. Wright, Francesco Cucca, Evan Tzanis, Caterina Barbieri, Jaakko Tuomilehto, Louise V. Wain, Jonathan Marten, James F. Wilson, Christopher Newton-Cheh, Reedik Mägi, Olli T. Raitakari, Peter W.F. Wilson, Joris Deelen, Morris Brown, Anna Morgan, Nabi Shah, Weihua Zhang, Ganesh Chauhan, Gail Davies, Peter S. Braund, Bram P. Prins, Alison Pattie, Marcus Dörr, Zoltán Kutalik, Marco Brumat, Franco Giulianini, Rainer Rettig, Uwe Völker, Georgios Ntritsos, Teresa Nutile, Todd L. Edwards, Albertine J. Oldehinkel, Christopher J. O'Donnell, Jaume Marrugat, Evangelos Evangelou, Nilesh J. Samani, Pekka Jousilahti, Dorret I. Boomsma, Harry Campbell, Francis S. Collins, Tim D. Spector, Simon Thom, Sarah E. Harris, Heather J. Cordell, Helen R. Warren, Cinzia Sala, Peter P. Pramstaller, Seppo Koskinen, Paul F. O'Reilly, Aravinda Chakravarti, Joshua C. Bis, Archie Campbell, Bernard Keavney, Sébastien Thériault, Gonneke Willemsen, Lynda M. Rose, Massimiliano Cocca, Jennifer E. Huffman, Meixia Ren, Massimo Mangino, Markus Perola, Joanna M. M. Howson, David Mosen-Ansorena, Harriëtte Riese, Martin Farrall, Albert V. Smith, Lenore J. Launer, Marina Ciullo, Antti-Pekka Sarin, Veikko Salomaa, Ilaria Gandin, Kent D. Taylor, Peter S. Sever, Markku Laakso, André G. Uitterlinden, Yan V. Sun, Raymond Noordam, Renée de Mutsert, Alan L. James, Jing Hua Zhao, Stefan Enroth, Andrew D. Morris, David S. Siscovick, Andrew D. Johnson, Igor Rudan, Tõnu Esko, Jun Ding, David P. Strachan, Martin D. Tobin, Christopher P. Nelson, Daniela Toniolo, J. Wouter Jukema, Vilmundur Gudnason, Borbala Mifsud, Marty Larson, Andrew A. Hicks, Adriana M. Hung, Antonietta Robino, Ruifang Li-Gao, Paul Elliott, Anne U. Jackson, Michela Traglia, Martin H. de Borst, Germaine C. Verwoert, Rheinhold Schmidt, Fabiola M Del Greco, Åsa Johansson, Anders Hamsten, Csaba P. Kovesdy, Mark J. Caulfield, Cumhur Y Demirkale, John M. C. Connell, Jian'an Luan, K. Witkowska, Georg Ehret, Cecilia M. Lindgren, Oscar H. Franco, Yongmei Liu, Ioanna Tzoulaki, Eric Boerwinkle, Catharina A. Hartman, Muralidharan Sargurupremraj, Claudia Langenberg, J. Michael Gaziano, Peter K. Joshi, Cornelia M. van Duijn, Maris Laan, Nick Shrine, Peter J. van der Most, Michael Boehnke, Leo-Pekka Lyytikäinen, Samuli Ripatti, Ben A. Oostra, Robert A. Scott, Lingchan Lu, Edward G. Lakatta, Yasaman Saba, Daniel Levy, Li Lin, Harold Schneider, Alex S. F. Doney, Michael R. Barnes, Najaf Amin, Hugh Watkins, Paul M. Ridker, Janina S Reid, Ayush Giri, Sekar Kathiresan, Lorna M. Lopez, Mike A. Nalls, Marina Evangelou, Erik Ingelsson, Lili Milani, Alice Stanton, Ozren Polasek, Sara M. Willems, Colin N. A. Palmer, Stéphanie Debette, Dan E. Arking, Helena Schmidt, Paul Knekt, John M. Starr, Yong Qian, Cristina Menni, Yuri Milaneschi, Christophe Tzourio, Tamara B. Harris, Kristin L. Ayers, Peter Vollenweider, Paolo Gasparini, Dennis O. Mook-Kanamori, Rodney J. Scott, Sandosh Padmanabhan, Anubha Mahajan, Peter Almgren, Jacklyn N. Hellwege, Teemu J. Niiranen, Mika Kähönen, Shih-Jen Hwang, Elizabeth G. Holliday, Edith Hofer, Priyanka Nandakumar, Peter J. Munson, Rick Jansen, Andrew P. Morris, Walter Palmas, Ilja M. Nolte, Siim Sõber, Thibaud Boutin, Ahmad Vaez, Albert Hofman, He Gao, Brenda W.J.H. Penninx, Neil Poulter, Alan J. Gow, Caroline Hayward, Nicholas J. Wareham, Elin Org, Philip S. Tsao, Claudia P. Cabrera, Aki S. Havulinna, Dragana Vuckovic, Kelly Cho, Jie Yao, Lars Lind, Jerome I. Rotter, David J. Stott, Ivana Kolcic, Wei-Yu Lin, Tatijana Zemunik, Tineka Blake, Kenneth Rice, Veronique Vitart, Alanna C. Morrison, Kay-Tee Khaw, Marjo-Riitta Järvelin, Guillaume Paré, Jouke-Jan Hottenga, Giorgia Girotto, Chiara Batini, Niki Dimou, Stella Trompet, John Danesh, Annette Peters, Alexander Teumer, Ulf Gyllensten, Joanne Knight, Vilmantas Giedraitis, Morris A. Swertz, Jaspal S. Kooner, Niek Verweij, Ibrahim Karaman, Murielle Bochud, Christian Gieger, Ruth J. F. Loos, Daniella Ruggiero, Arno Palotie, David Conen, Raha Pazoki, Denis C. Shields, Rossella Sorice, Philippe Amouyel, Gonçalo R. Abecasis, Andres Metspalu, John Attia, Bruce M. Psaty, Sarah H. Wild, Patricia B. Munroe, Daniel I. Chasman, Ollie Melander, John C. Chambers, Roby Joehanes, Eleftheria Zeggini, Johan Sundström, Chrysovalanto Mamasoula, Benjamin Lehne, Kati Kristiansson, Christopher Oldmeadow, Eco J. C. de Geus, A. Mesut Erzurumluoglu, Anuj Goel, Adam S. Butterworth, Digna R. Velez Edwards, Xiuqing Guo, Antti Jula, Praveen Surendran, Terho Lehtimäki, Mattias Frånberg, Teresa Ferreira, Ian J. Deary, David C. Liewald, Pim van der Harst, Erwin P. Bottinger, Roberto Elosua, and Fu Liang Ng
Subjects: Genetics, 0303 health sciences, Diastole, Disease, 030204 cardiovascular system & hematology, Biology, Precision medicine, Genetic analysis, 3. Good health, Pulse pressure, 03 medical and health sciences, 0302 clinical medicine, Blood pressure, Disease prevention, 030304 developmental biology, Genetic association
Abstract: High blood pressure is the foremost heritable global risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits to date (systolic, diastolic, pulse pressure) in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared loci influencing lifestyle exposures. Our findings offer the potential for a precision medicine strategy for future cardiovascular disease prevention.
Published: 2017

202. An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Author: Katri Räikkönen, Myriam Fornage, Jianxin Shi, Najaf Amin, Dale R. Nyholt, Jordan W. Smoller, Tõnu Esko, Wei Zhao, Carsten Horn, Andres Metspalu, Harold Snieder, Enrique Castelao, Luigi Ferrucci, Catharina A. Hartman, Thomas G. Schulze, Stanley I. Shyn, Joanne M. Murabito, James B. Potash, Cathryn M. Lewis, Karestan C. Koenen, Azmeraw T. Amare, Jari Lahti, Stephan Ripke, Michele L. Pergadia, Cornelia M. van Duijn, Michael Conlon O'Donovan, Markus M. Nöthen, Grant C.B. Sinnamon, Rudolf Uher, Roy H. Perlis, Qingqin S. Li, Hans-Jörgen Grabe, Johannes H. Smit, Bernhard T. Baune, Donald J. MacIntyre, Erin C. Dunn, Alexander Teumer, Gonneke Willemsen, Nicholas G. Martin, Udo Dannlowski, Karin Hek, Shaun Purcell, Toni-Kim Clarke, Toshiko Tanaka, Jorge A. Quiroz, Myrna M. Weissman, Andrew M. McIntosh, Kathryn L. Lunetta, Scott D. Gordon, David R. Weir, Daniel Umbricht, Marcella Rietschel, Zoltán Kutalik, Stephanie Williams, Michael Gill, Albert Hofman, Enrico Domenici, Margarita Rivera, Pamela A. F. Madden, Jingyun Yang, John P. Rice, Sandra Van der Auwera, Steven P. Hamilton, Georg Homuth, David A. Bennett, Stefan Kloiber, Sharon L.R. Kardia, Anders D. Børglum, Sven Cichon, Nese Direk, Jessica D. Faul, Susanne Lucae, Dorret I. Boomsma, Douglas Blackwood, Jouke-Jan Hottenga, Marilyn C. Cornelis, Erin B. Ware, Enda M. Byrne, Andrew C. Heath, Philip L. De Jager, Ole Mors, Karl-Heinz Ladwig, Bertram Müller-Myhsok, Thomas H. Mosley, Jennifer A. Smith, Tracy Air, Yuri Milaneschi, Glyn Lewis, Brenda W.J.H. Penninx, David J. Llewellyn, Gerard van Grootheest, Eco J. C. de Geus, Henning Tiemeier, Grant W. Montgomery, Martin Preisig, Katherine E. Tansey, Patrick F. Sullivan, Douglas F. Levinson, Henriette N. Buttenschøn, Gerome Breen, Johan G. Eriksson, Ayse Demirkan, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, APH - Methodology, APH - Digital Health, Epidemiology, Child and Adolescent Psychiatry / Psychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Medicum, Department of Psychology and Logopedics, and Developmental Psychology Research Group
Subjects: DISORDER, Netherlands Twin Register (NTR), Linkage disequilibrium, SYMPTOMS, STRESS, CHARGE consortium, genetics [Depressive Disorder], Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, Neoplasm Proteins/genetics, MINOR DEPRESSION, European Continental Ancestry Group/genetics, POPULATION, RISK, Genetics, education.field_of_study, HERITABILITY, Depression, Depressive symptoms, Depression/genetics, Acid Anhydride Hydrolases, Neoplasm Proteins, 3. Good health, genetics [European Continental Ancestry Group], Phenotype, fragile histidine triad protein, Major depressive disorder, genetics [Depression], Psychology, 515 Psychology, Population, genetics [White People], Single-nucleotide polymorphism, Locus (genetics), White People, Psychiatric Genomics Consortium, FHIT gene, 03 medical and health sciences, SDG 3 - Good Health and Well-being, ddc:570, Depressive Disorder/genetics, NATIONAL COMORBIDITY SURVEY, medicine, Journal Article, Humans, SNP, genetics [Acid Anhydride Hydrolases], Genetic Predisposition to Disease, ddc:610, education, Biological Psychiatry, Genetic association, Depressive Disorder, genetics [Neoplasm Proteins], major depressive disorder, 3112 Neurosciences, MAJOR DEPRESSION, medicine.disease, SUBTHRESHOLD DEPRESSION, 030227 psychiatry, Acid Anhydride Hydrolases/genetics, Genetic Loci, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10(-9)) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10(-9)).CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
Published: 2017

203. Erratum

Author: Deepali Jaju, Melanie Neijts, Gabrielle Boucher, Arpi Minassian, James D. Stewart, Andreas Voss, Pim van der Harst, Duanping Liao, Joshua C. Bis, Kari E. North, Matteo Barcella, Michel G. Nivard, Jitender Kumar, Andrew Wong, Dewleen G. Baker, G. Ehret, Sulayma Albarwani, Kathleen F. Kerr, Quenna Wong, Ville Huikari, Alexander Kluttig, Andrew P. Morris, Eco J. C. de Geus, Albertine J. Oldehinkel, Ann-Christine Syvänen, Martina Mueller-Nurasyid, Yong Li, Marcel den Hoed, Henning Tiemeier, Henriette E. Meyer zu Schwabedissen, Dorret I. Boomsma, Joop D. Lefrandt, Mohammad Hadi Zafarmand, Victoria B. Risbrough, Halina Greiser, Bruce M. Psaty, Oscar H. Franco, Niek Verweij, Cees A. Swenne, Antti M. Kiviniemi, Konstantin Strauch, Markus Juonala, Zhu Ming Zhang, Nicholas L. Smith, Olli T. Raitakari, Daiane Hemerich, Daniel T. O'Connor, Christopher J. O'Donnell, Riad Bayoumi, Peter Friberg, Alvaro Alonso, Julian F. Thayer, Caroline M. Nievergelt, Delilah Zabaneh, Steven A. Lubitz, Tomas Axelsson, Terho Lehtimäki, Daniele Cusi, Eric A. Whitsel, Arie M. van Roon, Kjell Nikus, Bruno H. Stricker, Bouwe P. Krijthe, Stefan Kääb, Lars Lind, Abdel Abdellaoui, Timothy A. Thornton, Anubha Mahajan, Johan Sundström, Nona Sotoodehnia, Charles Kooperberg, Moritz F. Sinner, Leo-Pekka Lyytikäinen, Xavier Jouven, Tanja G. M. Vrijkotte, Sander W. van der Laan, Tatiana Kuznetsova, Patrick T. Ellinor, Alexander P. Reiner, Ilja M. Nolte, Marian C. Limacher, Paul I.W. de Bakker, Ahmad Vaez, Albert Hofman, Meena Kumari, Folkert W. Asselbergs, Juhani Junttila, Bram Dierckx, Marjo-Riitta Järvelin, Ingrid E. Christophersen, Annie Britton, Cathy C. Laurie, Phyllis K. Stein, Katarzyna Stolarz-Skrzypek, Juha Auvinen, Alexander Teumer, Vilmantas Giedraitis, Foram N. Ashar, Jenny van Dongen, David S. Siscovick, Markku Eskola, Jussi Hernesniemi, Janine F. Felix, M. Loretto Munoz, Jessica van Setten, Yun Li, Bianca J. J. M. Brundel, Christine M. Albert, Annette Peters, Jerome I. Rotter, Nina Hutri-Kähönen, Mark A. Geyer, Lesley E. Tinker, Vinicius Tragante, Susan R. Heckbert, Alan B. Zonderman, John D. Rioux, Kent D. Taylor, Shih-Jen Hwang, Johan Ormel, Mike A. Nalls, Erik Ingelsson, Kirk C. Wilhelmsen, John S. Floras, Diana Kuh, Elsayed Z. Soliman, Henry J. Lin, Brenda W.J.H. Penninx, Mika Kivimäki, Maaike G. J. Gademan, Jouke-Jan Hottenga, Mika Kähönen, Gerjan Navis, Siegfried Perz, Tamar Sofer, Catharina A. Hartman, Barbara McKnight, Jan A. Kors, Rick Jansen, Melanie Waldenberger, Nina Mononen, Heikki V. Huikuri, Azmeraw T. Amare, Mohammad L. Hassan, Jan A. Staessen, Adam X. Maihofer, Erika Salvi, Rob J. Bieringa, Benedikt von der Heyde, Andrea Dietrich, Peter J. van der Most, Philippe Goyette, Harriëtte Riese, Michele K. Evans, Stephanie M. Gogarten, Jean-Claude Tardif, Harold Snieder, Adrienne M. Stilp, Christy L. Avery, Johannes H. Smit, Gonneke Willemsen, Yuri Milaneschi, André G. Uitterlinden, Cecilia M. Lindgren, VU University medical center, APH - Mental Health, Psychiatry, Physiology, ACS - Heart failure & arrhythmias, APH - Methodology, and APH - Digital Health
Subjects: 0301 basic medicine, Genetics, Multidisciplinary, Science, General Physics and Astronomy, General Chemistry, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Disease risk, Heart rate variability, 030217 neurology & neurosurgery
Abstract: Nature Communications 8: Article number: 15805 (2017); Published: 14 June 2017; Updated: 2 August 2017 In Supplementary Fig. 10 of this Article, images for panels a and b were inadvertently omitted. The correct version of Supplementary Fig. 10 is provided as Supplementary Information associated withthis Erratum.
Published: 2017

204. Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

Author: Jan H. Smit, Erik A. Ehli, Gareth E. Davies, Brenda W.J.H. Penninx, Yuri Milaneschi, Dorret I. Boomsma, Eco J. C. de Geus, Gonneke Willemsen, Lannie Ligthart, Jouke-Jan Hottenga, Hamdi Mbarek, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, APH - Methodology, APH - Digital Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), medicine.medical_specialty, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, medicine, Journal Article, SNP, Humans, Psychiatry, Gene, Genetics (clinical), Chromosome 7 (human), Genetics, Depressive Disorder, Major, Neuropeptides, Obstetrics and Gynecology, medicine.disease, Cytoskeletal Proteins, 030104 developmental biology, Genome wide significance, Pediatrics, Perinatology and Child Health, Major depressive disorder, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10−8) and gene-based (p = 1.48 × 10−7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.
Published: 2017

205. Polygenic risk for alcohol consumption and its association with alcohol-related phenotypes: Do stress and life satisfaction moderate these relationships?

Author: Jorien L. Treur, Gonneke Willemsen, Karin J. H. Verweij, Jacqueline M. Vink, Dorret I. Boomsma, Lannie Ligthart, Iryna O. Fedko, Gabry W. Mies, Jouke-Jan Hottenga, Meike Bartels, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Methodology
Subjects: Netherlands Twin Register (NTR), 0301 basic medicine, Adult, Male, Multifactorial Inheritance, Adolescent, Alcohol Drinking, Alcohol, Genome-wide association study, Personal Satisfaction, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Risk Factors, Journal Article, Genetic predisposition, Medicine, Humans, Pharmacology (medical), Young adult, Gene–environment interaction, Generalized estimating equation, Aged, Netherlands, Pharmacology, Aged, 80 and over, Alcohol Use Disorders Identification Test, business.industry, Life satisfaction, Middle Aged, 3. Good health, Psychiatry and Mental health, Alcoholism, 030104 developmental biology, Phenotype, chemistry, Female, Gene-Environment Interaction, business, Developmental Psychopathology, 030217 neurology & neurosurgery, Stress, Psychological, Demography, Genome-Wide Association Study
Abstract: Contains fulltext : 179407.pdf (Publisher’s version ) (Closed access) Background: Genetic and environmental factors contribute about equally to alcohol-related phenotypes in adulthood. In the present study, we examined whether more stress at home or low satisfaction with life might be associated with heavier drinking or more alcohol-related problems in individuals with a high genetic susceptibility to alcohol use. Methods: Information on polygenic scores and drinking behavior was available in 6705 adults (65% female; 18-83 years) registered with the Netherlands Twin Register. Polygenic risk scores (PRSs) were constructed for all subjects based on the summary statistics of a large genome-wide association meta-analysis on alcohol consumption (grams per day). Outcome measures were quantity of alcohol consumption and alcohol-related problems assessed with the Alcohol Use Disorders Identification Test (AUDIT). Stress at home and life satisfaction were moderating variables whose significance was tested by Generalized Estimating Equation analyses taking familial relatedness, age and sex into account. Results: PRSs for alcohol were significantly associated with quantity of alcohol consumption and alcohol-related problems in the past year (R2 = 0.11% and 0.10% respectively). Participants who reported to have experienced more stress in the past year and lower life satisfaction, scored higher on alcohol-related problems (R2 = 0.27% and 0.29 respectively), but not on alcohol consumption. Stress and life satisfaction did not moderate the association between PRSs and the alcohol outcome measures. Conclusions: There were significant main effects of polygenic scores and of stress and life satisfaction on drinking behavior, but there was no support for PRS-by-stress or PRS-by-life satisfaction interactions on alcohol consumption and alcohol-related problems. 6 p.
Published: 2017

206. Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney

Author: Peter Vollenweider, Christophe Tzourio, Stefan Enroth, Cinzia Sala, Mark J. Caulfield, Murielle Bochud, Peter P. Pramstaller, Ozren Polasek, Paul Elliott, Dennis O. Mook-Kanamori, Daniel I. Chasman, Christian Gieger, Harriëtte Riese, Rodney J. Scott, Cristina Menni, Anubha Mahajan, Elizabeth G. Holliday, Ilja M. Nolte, Priyanka Nandakumar, Tatijana Zemunik, Dragana Vuckovic, Tõnu Esko, Franco Giulianini, Michael Boehnke, Antonietta Robino, Anne U. Jackson, Roby Joehanes, Alanna C. Morrison, Kay-Tee Khaw, Alison Pattie, Peter J. van der Most, Mika Kähönen, Rick Jansen, Andrew D. Johnson, John M. Starr, Marcus Dörr, Anders Hamsten, Kenneth Rice, Alice Stanton, James F. Wilson, Nabi Shah, Weihua Zhang, Andrew A. Hicks, Jeffrey Damman, Jing Hua Zhao, Aarno Palotie, Veronique Vitart, Alan J. Gow, Caroline Hayward, Alan James, Ben A. Oostra, Janina S. Ried, John Beilby, David P. Strachan, Martin D. Tobin, Eco J. C. de Geus, Vilmundur Gudnason, Bruce M. Psaty, Zoltán Kutalik, Neil Poulter, Paul M. Ridker, Johan Sundström, Cornelia M. van Duijn, Eleftheria Zeggini, Christopher Oldmeadow, Borbala Mifsud, Giorgia Girotto, Aravinda Chakravarti, Jonathan Marten, Alexander Teumer, Joanne Knight, Robert A. Scott, Vilmantas Giedraitis, Paul F. O'Reilly, Marco Brumat, Brenda W.J.H. Penninx, Peter J. Munson, Olli T. Raitakari, Leo-Pekka Lyytikäinen, He Gao, Massimo Mangino, Benjamin Lehne, J. Wouter Jukema, Paul Knekt, Catharina A. Hartman, Rona J. Strawbridge, Jouke-Jan Hottenga, Jaspal S. Kooner, Nilesh J. Samani, Kristin L. Ayers, A. Mesut Erzurumluoglu, Joshua C. Bis, Archie Campbell, Dan E. Arking, Germaine C. Verwoert, John Attia, Samuli Ripatti, Yuri Milaneschi, Caterina Barbieri, Fabiola M. Del Greco, C M Lindgren, Peter K. Joshi, Helen R. Warren, Nicholas J. Wareham, Simon Thom, Seppo Koskinen, Tamara B. Harris, Ilaria Gandin, Kent D. Taylor, Andrew D. Morris, Anna Morgan, Chiara Batini, Terho Lehtimäki, Walter Palmas, David Conen, Harold Snieder, Martin H. de Borst, Sarah E. Harris, Igor Rudan, Ruth J. F. Loos, Claudia Langenberg, Anuj Goel, Christopher P. Nelson, Peter S. Braund, Rossella Sorice, Yasaman Saba, Oscar H. Franco, Yongmei Liu, Mattias Frånberg, David S. Siscovick, Patricia B. Munroe, Rainer Rettig, Michela Traglia, Daniel Levy, Li Lin, Michael R. Barnes, Elin Org, Anne-Claire Vergnaud, Andres Metspalu, Stéphanie Debette, Yusuf Demirkale, John M. C. Connell, Jian'an Luan, Paolo Gasparini, Tim D. Spector, Marina Ciullo, Antti-Pekka Sarin, Ian J. Deary, Teemu J. Niiranen, Marty Larson, Heather J. Cordell, Jerome I. Rotter, Sekar Kathiresan, Teresa Nutile, Andrew P. Morris, Denis C. Shields, Alan F. Wright, Lorna M. Lopez, Aki S. Havulinna, Gonçalo R. Abecasis, Edith Hofer, Siim Sõber, Sébastien Thériault, Ahmad Vaez, Albert Hofman, Gonneke Willemsen, Lynda M. Rose, John C. Chambers, Peter S. Sever, Maryam Abedi, André G. Uitterlinden, François Mach, Massimiliano Cocca, Sarah H Wild, Reinhold Schmidt, Jaume Marrugat, Marc A. Seelen, Maris Laan, Aude Saint Pierre, David C. Liewald, Pim van der Harst, Sandosh Padmanabhan, Martin Farrall, Georg Ehret, Albert V. Smith, Quang Tri Nguyen, Ulf Gyllensten, Helena Schmidt, Ganesh Chauhan, Jennifer E. Huffman, Morris A. Swertz, Jaakko Tuomilehto, Louise V. Wain, Meixia Ren, Erwin P. Bottinger, Roberto Elosua, Ivana Kolcic, Veikko Salomaa, Stella Trompet, Bernard Keavney, Claudia P. Cabrera, Bram P. Prins, Jennie Hui, Uwe Völker, Albertine J. Oldehinkel, Evangelos Evangelou, Pekka Jousilahti, Dorret I. Boomsma, Harry Campbell, Shih-Jen Hwang, Jie Yao, Francis S. Collins, Chrysovalanto Mamasoula, Kati Kristiansson, Markus Perola, Renée de Mutsert, Xiuqing Guo, Antti Jula, Daniela Toniolo, Ruifang Li-Gao, Åsa Johansson, Nick Shrine, Teresa Ferreira, Lars Lind, David J. Stott, Tineka Blake, Daniela Ruggiero, Mike A. Nalls, Erik Ingelsson, Colin N. A. Palmer, Christopher Newton-Cheh, Marjo-Riitta Järvelin, Guillaume Paré, Joris Deelen, Morris Brown, Gail Davies, Annette Peters, Ioanna Tzoulaki, Alex S. F. Doney, Najaf Amin, Lenore J. Launer, Hugh Watkins, Yingchang Lu, Wain, Lv, Vaez, A, Jansen, R, Joehanes, R, van der Most, Pj, Erzurumluoglu, Am, O'Reilly, Pf, Cabrera, Cp, Warren, Hr, Rose, Lm, Verwoert, Gc, Hottenga, Jj, Strawbridge, Rj, Esko, T, Arking, De, Hwang, Sj, Guo, X, Kutalik, Z, Trompet, S, Shrine, N, Teumer, A, Ried, J, Bis, Jc, Smith, Av, Amin, N, Nolte, Im, Lyytikäinen, Lp, Mahajan, A, Wareham, Nj, Hofer, E, Joshi, Pk, Kristiansson, K, Traglia, M, Havulinna, A, Goel, A, Nalls, Ma, Sõber, S, Vuckovic, Dragana, Luan, J, Del Greco, M. F, Ayers, Kl, Marrugat, J, Ruggiero, D, Lopez, Lm, Niiranen, T, Enroth, S, Jackson, Au, Nelson, Cp, Huffman, Je, Zhang, W, Marten, J, Gandin, I, Harris, Se, Zemunik, T, Lu, Y, Evangelou, E, Shah, N, de Borst, Mh, Mangino, M, Prins, Bp, Campbell, A, Li Gao, R, Chauhan, G, Oldmeadow, C, Abecasis, G, Abedi, M, Barbieri, Cm, Barnes, Mr, Batini, C, Beilby, J, Blake, T, Boehnke, M, Bottinger, Ep, Braund, P, Brown, M, Brumat, M, Campbell, H, Chambers, Jc, Cocca, M, Collins, F, Connell, J, Cordell, Hj, Damman, Jj, Davies, G, de Geus, Ej, de Mutsert, R, Deelen, J, Demirkale, Y, Doney, Asf, Dörr, M, Farrall, M, Ferreira, T, Frånberg, M, Gao, H, Giedraitis, V, Gieger, C, Giulianini, F, Gow, Aj, Hamsten, A, Harris, Tb, Hofman, A, Holliday, Eg, Hui, J, Jarvelin, Mr, Johansson, Å, Johnson, Ad, Jousilahti, P, Jula, A, Kähönen, M, Kathiresan, S, Khaw, Kt, Kolcic, I, Koskinen, S, Langenberg, C, Larson, M, Launer, Lj, Lehne, B, Liewald, Dcm, Lin, L, Lind, L, Mach, F, Mamasoula, C, Menni, C, Mifsud, B, Milaneschi, Y, Morgan, Anna, Morris, Ad, Morrison, Ac, Munson, Pj, Nandakumar, P, Nguyen, Qt, Nutile, T, Oldehinkel, Aj, Oostra, Ba, Org, E, Padmanabhan, S, Palotie, A, Paré, G, Pattie, A, Penninx, Bwjh, Poulter, N, Pramstaller, Pp, Raitakari, Ot, Ren, M, Rice, K, Ridker, Pm, Riese, H, Ripatti, S, Robino, A, Rotter, Ji, Rudan, I, Saba, Y, Saint Pierre, A, Sala, Cf, Sarin, Ap, Schmidt, R, Scott, R, Seelen, Ma, Shields, Dc, Siscovick, D, Sorice, R, Stanton, A, Stott, Dj, Sundström, J, Swertz, M, Taylor, Kd, Thom, S, Tzoulaki, I, Tzourio, C, Uitterlinden, Ag, Völker, U, Vollenweider, P, Wild, S, Willemsen, G, Wright, Af, Yao, J, Thériault, S, Conen, D, Attia, J, Sever, P, Debette, S, Mook Kanamori, Do, Zeggini, E, Spector, Td, van der Harst, P, Palmer, Cna, Vergnaud, Ac, Loos, Rjf, Polasek, O, Starr, Jm, Girotto, Giorgia, Hayward, C, Kooner, J, Lindgren, Cm, Vitart, V, Samani, Nj, Tuomilehto, J, Gyllensten, U, Knekt, P, Deary, Ij, Ciullo, M, Elosua, R, Keavney, Bd, Hicks, Aa, Scott, Ra, Gasparini, Paolo, Laan, M, Liu, Y, Watkins, H, Hartman, Ca, Salomaa, V, Toniolo, D, Perola, M, Wilson, Jf, Schmidt, H, Zhao, Jh, Lehtimäki, T, van Duijn, Cm, Gudnason, V, Psaty, Bm, Peters, A, Rettig, R, James, A, Jukema, Jw, Strachan, Dp, Palmas, W, Metspalu, A, Ingelsson, E, Boomsma, Di, Franco, Oh, Bochud, M, Newton Cheh, C, Munroe, Pb, Elliott, P, Chasman, Di, Chakravarti, A, Knight, J, Morris, Ap, Levy, D, Tobin, Md, Snieder, H, Caulfield, Mj, Ehret, G. b., Home Office, Medical Research Council (MRC), National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, British Heart Foundation, Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), Lifestyle Medicine (LM), Vascular Ageing Programme (VAP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Institute for Organ Transplantation (GIOT), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Epidemiology, Gastroenterology & Hepatology, Clinical Genetics, Internal Medicine, Erasmus MC other, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Epidemiology and Data Science, Division 6, APH - Mental Health, APH - Digital Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Methodology
Subjects: 0301 basic medicine, cardiovascular risk, Netherlands Twin Register (NTR), hypertension, NETHERLANDS, Sistema cardiovascular -- Malalties, GWAS, blood pressure, complex traits, eSNP, Locus (genetics), Genome-wide association study, Disease, Biology, PERIPHERAL-BLOOD, 1102 Cardiovascular Medicine And Haematology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, Internal Medicine, Journal Article, Cardiac and Cardiovascular Systems, 1000 Genomes Project, Gene, CENTRIC ARRAY, METAANALYSIS, Genetics, ddc:616, Kardiologi, PULSE PRESSURE, COMMON VARIANTS, 1103 Clinical Sciences, ta3121, 3. Good health, INDIVIDUALS, 030104 developmental biology, Blood pressure, TARGET, Cardiovascular System & Hematology, complex trait, GWAS, blood pressure, cardiovascular risk, complex traits, eSNP, hypertension, Hipertensió, Imputation (genetics), TRAITS
Abstract: Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project–based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7 , TNXB , LRP12 , LOC283335 , SEPT9 , and AKT2 , and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA . Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
Published: 2017

207. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author: Gerjan Navis, Moritz F. Sinner, Kathleen F. Kerr, Heikki V. Huikuri, Daniele Cusi, Oscar H. Franco, Marian C. Limacher, Charles Kooperberg, Gabrielle Boucher, Riad Bayoumi, Juhani Junttila, Ann-Christine Syvänen, Andrew P. Morris, Anubha Mahajan, Andreas Voss, Paul I.W. de Bakker, Patrick T. Ellinor, Phyllis K. Stein, Janine F. Felix, Mark A. Geyer, Mike A. Nalls, Erik Ingelsson, Vinicius Tragante, Joshua C. Bis, Kari E. North, Jean-Claude Tardif, Harold Snieder, Azmeraw T. Amare, Katarzyna Stolarz-Skrzypek, Markku Eskola, Ilja M. Nolte, Tanja G. M. Vrijkotte, Elsayed Z. Soliman, Deepali Jaju, Melanie Neijts, Adrienne M. Stilp, Mika Kähönen, Henry J. Lin, Jessica van Setten, Meena Kumari, Halina Greiser, John S. Floras, Henriette E. Meyer zu Schwabedissen, Mohammad Hadi Zafarmand, Dewleen G. Baker, Rick Jansen, Cathy C. Laurie, Matteo Barcella, Christy L. Avery, Stefan Kääb, Michel G. Nivard, Jitender Kumar, Lars Lind, Alexander Teumer, Johan Sundström, Kirk C. Wilhelmsen, Barbara McKnight, Vilmantas Giedraitis, Johannes H. Smit, Gonneke Willemsen, Nona Sotoodehnia, Michele K. Evans, Christine M. Albert, Kent D. Taylor, Marcel den Hoed, James D. Stewart, Peter Friberg, Alvaro Alonso, Susan R. Heckbert, Kjell Nikus, Siegfried Perz, André G. Uitterlinden, Bruce M. Psaty, Antti M. Kiviniemi, G. Ehret, Jouke-Jan Hottenga, Sulayma Albarwani, Bouwe P. Krijthe, Timothy A. Thornton, Caroline M. Nievergelt, Delilah Zabaneh, Zhu Ming Zhang, Annie Britton, Ingrid E. Christophersen, Adam X. Maihofer, Juha Auvinen, David S. Siscovick, Arie M. van Roon, Xavier Jouven, Stephanie M. Gogarten, M. Loretto Munoz, Erika Salvi, Folkert W. Asselbergs, Bram Dierckx, Marjo-Riitta Järvelin, Cecilia M. Lindgren, Yun Li, Quenna Wong, Alan B. Zonderman, Yuri Milaneschi, John D. Rioux, Brenda W.J.H. Penninx, Philippe Goyette, Niek Verweij, Harriëtte Riese, Bruno H. Stricker, Markus Juonala, Rob J. Bieringa, Arpi Minassian, Jenny van Dongen, Abdel Abdellaoui, Foram N. Ashar, Jan A. Kors, Albertine J. Oldehinkel, Jussi Hernesniemi, Sander W. van der Laan, Ahmad Vaez, Nina Hutri-Kähönen, Annette Peters, Lesley E. Tinker, Albert Hofman, Dorret I. Boomsma, Victoria B. Risbrough, Tamar Sofer, Pim van der Harst, Konstantin Strauch, Steven A. Lubitz, Catharina A. Hartman, Jerome I. Rotter, Shih-Jen Hwang, Duanping Liao, Mika Kivimäki, Mohammad L. Hassan, Andrew Wong, Peter J. van der Most, Alexander Kluttig, Nina Mononen, Eco J. C. de Geus, Henning Tiemeier, Benedikt von der Heyde, Martina Müller-Nurasyid, Joop D. Lefrandt, Andrea Dietrich, Nicholas L. Smith, Terho Lehtimäki, Bianca J. J. M. Brundel, Jan A. Staessen, Cees A. Swenne, Julian F. Thayer, Daniel T. O'Connor, Christopher J. O'Donnell, Eric A. Whitsel, Tatiana Kuznetsova, Alexander P. Reiner, Johan Ormel, Ville Huikari, Yong Li, Tomas Axelsson, Olli T. Raitakari, Daiane Hemerich, Leo-Pekka Lyytikäinen, Maaike G. J. Gademan, Melanie Waldenberger, Diana Kuh, Ehret, Georg Benedikt, APH - Personalized Medicine, APH - Global Health, Other Research, ACS - Amsterdam Cardiovascular Sciences, Public and occupational health, APH - Methodology, APH - Health Behaviors & Chronic Diseases, ARD - Amsterdam Reproduction and Development, APH - Aging & Later Life, ACS - Atherosclerosis & ischemic syndromes, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Physiology, ACS - Heart failure & arrhythmias, APH - Digital Health, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Vascular Ageing Programme (VAP), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Value, Affordability and Sustainability (VALUE), Biological Psychology, Praxis, Environmental Geography (former), Child and Adolescent Psychiatry / Psychology, Rheumatology, Epidemiology, Medical Informatics, and Internal Medicine
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Medicin och hälsovetenskap, Potassium Channels, Chemistry(all), Muscle Proteins, General Physics and Astronomy, Genome-wide association study, Blood Pressure, PEDIGREES, Bioinformatics, Biochemistry, Genome-wide association studies, Medical and Health Sciences, Cohort Studies, Heart Rate, Risk Factors, RGS Proteins/genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, RECORDINGS, Heart rate variability, Vagal tone, European Continental Ancestry Group/genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics, ddc:616, Muscle Proteins/genetics, Multidisciplinary, digestive, oral, and skin physiology, Single Nucleotide, Multidisciplinary Sciences, Science & Technology - Other Topics, Heart Diseases/genetics/physiopathology, Erratum, circulatory and respiratory physiology, Heart Diseases, Science, Quantitative Trait Loci, RESPIRATORY SINUS ARRHYTHMIA, Quantitative trait locus, Biology, Physics and Astronomy(all), Polymorphism, Single Nucleotide, White People, General Biochemistry, Genetics and Molecular Biology, Article, PARASYMPATHETIC REGULATION, 03 medical and health sciences, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Heart rate, Journal Article, Humans, Genetic Predisposition to Disease, COHORT, Polymorphism, GENOME-WIDE ASSOCIATION, METAANALYSIS, Genetic association, MODULATOR, Science & Technology, Biochemistry, Genetics and Molecular Biology(all), MORTALITY, Cardiovascular genetics, General Chemistry, Membrane hyperpolarization, ta3121, 030104 developmental biology, Expression quantitative trait loci, ATRIAL-FIBRILLATION, Potassium Channels/genetics, RGS Proteins, Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract: Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74, Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.
Published: 2017

208. Erratum to 'Short communication: Genetic association between schizophrenia and cannabis use' [Drug Alcohol Depend. 171 (2017) 117-121]

Author: Abdel Abdellaoui, Jouke-Jan Hottenga, Dorret I. Boomsma, Karin J. H. Verweij, Harmen H.M. Draisma, Lannie Ligthart, Nathan A. Gillespie, Michel G. Nivard, Camelia C. Minică, Gonneke Willemsen, Alberto Sainz Cort, and Jacqueline M. Vink
Subjects: Drug, medicine.medical_specialty, media_common.quotation_subject, MEDLINE, Toxicology, 17 Psychology And Cognitive Sciences, 03 medical and health sciences, 0302 clinical medicine, medicine, International Cannabis Consortium, Pharmacology (medical), Psychiatry, media_common, Genetic association, Pharmacology, biology, Published Erratum, Substance Abuse, 11 Medical And Health Sciences, Cannabis use, biology.organism_classification, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Schizophrenia, Cannabis, Psychology, Developmental Psychopathology, 030217 neurology & neurosurgery
Abstract: The publisher regrets that in the online version of this article, authors Nathan A. Gillespie, Gonneke Willemsen, Jouke-Jan Hottenga, Dorret I. Boomsma and Jacqueline M. Vink were omitted from the author list. The correct list of authors is shown below: Karin J.H. Verweij∗, Abdel Abdellaoui, Michel G. Nivard, Alberto Sainz Cort, LannieLigthart, Harmen H.M. Draisma, Camelia C. Minica, International Cannabis Consortium1, Nathan A. Gillespie, Gonneke Willemsen, Jouke-Jan Hottenga, Dorret I. Boomsma, Jacqueline M. Vink. The publisher would like to apologise for any inconvenience caused.
Published: 2017

209. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults

Author: Amélie Bonnefond, Nancy L. Heard-Costa, Julius S. Ngwa, Jennifer E. Huffman, Tanja B. Grammer, Jaakko Tuomilehto, Lu Qi, Nicholas G. Martin, Massimo Mangino, Henrik Vestergaard, Penny Gordon-Larsen, Reedik Mägi, Natalia V. Rivera, Charles Kooperberg, Alain G. Bertoni, Sarah H. Wild, Robert Luben, Veikko Salomaa, Claude Bouchard, Lynda M. Rose, Patricia A. Peyser, Graciela E. Delgado, Jessica D. Faul, Tuija Tammelin, John C. Chambers, Tsegaselassie Workalemahu, Kari E. North, David J. Porteous, Peter Vollenweider, Kennet Harald, Claire Bellis, Serena Sanna, Nicholas D. Hastie, Robert J. Klein, Marie-Claude Vohl, Ruth J. F. Loos, Jian Gong, Igor Rudan, Unhee Lim, Christopher A. Haiman, Martina Müller-Nurasyid, Konstantin Strauch, Mark A. Sarzynski, Albert V. Smith, Mark Walker, Tapani Ebeling, Göran Hallmans, Nicole Dueker, Caroline S. Fox, Sven Bergmann, Keri L. Monda, Thorkild I. A. Sørensen, André G. Uitterlinden, Johanne Marie Justesen, Aki S. Havulinna, Torben Hansen, Ivana Kolcic, Cecilia M. Lindgren, Marcel den Hoed, Richard N. Bergman, Mariaelisa Graff, Alan R. Shuldiner, Dorota Pasko, James F. Wilson, John Whitfield, Joel Eriksson, Jaspal S. Kooner, Mette Hollensted, Winfried März, Gonçalo R. Abecasis, Weihua Zhang, Harold Snieder, Rajesh Rawal, Tao Huang, Åsa Johansson, Lydia Quaye, Ying Wu, Benjamin Lehne, Matthias Nauck, Caroline Hayward, Linda S. Adair, Michel Marre, Tanguy Corre, Alan James, Frida Renström, Jian'an Luan, Zoltán Kutalik, Kurt Lohman, Jennifer A. Smith, Mao Fu, Jennifer L. Bragg-Gresham, Tamara B. Harris, Claudia Langenberg, Tõnu Esko, Mattias Lorentzon, Ken K. Ong, Blair H. Smith, Fabio Busonero, Alan F. Wright, Gemma Cadby, Andrew D. Johnson, Steve Buyske, Anubha Mahajan, Antonella Mulas, Gérard Waeber, Lori L. Bonnycastle, Daniel I. Chasman, Jennie Hui, Audrey Y. Chu, Uwe Völker, Albertine J. Oldehinkel, Jing Hua Zhao, Robert A. Scott, Ilja M. Nolte, Loic LeMarchand, Yu-Ching Cheng, David P. Strachan, Jie Huang, Gerard van Grootheest, John D. Eicher, Marcus E. Kleber, Francis S. Collins, Cornelia M. van Duijn, Timothy M. Frayling, Pau Navarro, Leo-Pekka Lyytikäinen, Cinzia Sarti, Paul M. Ridker, John-Olov Jansson, Shafqat Ahmad, Philippe Froguel, Albert Hofman, Inga Prokopenko, Vilmundur Gudnason, Anne U. Jackson, David R. Weir, Lyle J. Palmer, Alexander Teumer, Ulf Gyllensten, Mette Aadahl, Niels Grarup, Beverley Balkau, Oluf Pedersen, Cornelia Huth, Dorret I. Boomsma, Harry Campbell, Charlotte Huppertz, Ingrid B. Borecki, Juha Auvinen, Soren Snitker, Yuri Milaneschi, Iris M. Heid, Barbara Thorand, Wouter J. Peyrot, Lavinia Paternoster, Sian-Tsung Tan, Anne E. Justice, Dena G. Hernandez, Marcus Dörr, Nicholas J. Wareham, Marilyn C. Cornelis, Claes Ohlsson, Amy J. Swift, Ozren Polasek, Brenda W.J.H. Penninx, James E. Hayes, Stephanie A. Bien, Jana V. van Vliet-Ostaptchouk, Eric Boerwinkle, Louis Pérusse, Peter J. van der Most, Ulrike Peters, Pirjo Komulainen, Lynne J. Hocking, Catharina A. Hartman, William R. Scott, Jeffrey R. O'Connell, Stefania Bandinelli, Tuomo Rankinen, Timo A. Lakka, Leena Kinnunen, Markus Perola, John Blangero, Sharon L.R. Kardia, Veronique Vitart, Mika Kähönen, Marie Neergaard Harder, Diana Kuh, Kai Savonen, Kristin L. Young, Jeremiah Perez, Nina Hutri-Kähönen, George Davey Smith, Toshiko Tanaka, Barbara Sternfeld, Jennifer A. Nettleton, Jouke-Jan Hottenga, Christian Gieger, Gonneke Willemsen, Soren Brage, Mika Kivimäki, Lucia A. Hindorff, Steve Sidney, Tarunveer S. Ahluwalia, Liesbeth Vandenput, Loic Yengo, Markku Laakso, Yongmei Liu, Arthur W. Musk, Harald Grallert, Kirsti Kvaløy, Rainer Rauramaa, Satu Männistö, Tuomas O. Kilpeläinen, M. Carola Zillikens, Hannu Puolijoki, Luting Xue, Oddgeir L. Holmens, Sandosh Padmanabhan, Inês Barroso, Ching-Ti Liu, L. Adrienne Cupples, Judith B. Borja, Karen L. Mohlke, Matthias Olden, Henry Völzke, Myriam Fornage, Michael Boehnke, Pedro Marques-Vidal, John Beilby, Fernando Rivadeneira, Maija Hassinen, Najaf Amin, Kristian Hveem, Gudny Eiriksdottir, Lenore J. Launer, Johanna Kuusisto, Dorothée Thuillier, Heather M. Stringham, Sven Gläser, Min A. Jhun, Marjo-Riitta Järvelin, Niha Zubair, Annette Peters, Llilda Barata, Paula J. Griffin, Markus Juonala, Wei Zhao, Andres Metspalu, Christina Holzapfel, Lawrence F. Bielak, Thomas W. Winkler, Alena Stančáková, Anke Tönjes, Narisu Narisu, David Hadley, Peter S. Chines, Andrew Wong, Günther Silbernagel, Kati Kristiansson, Eco J. C. de Geus, Grant W. Montgomery, Elise Lim, Laura J. Rasmussen-Torvik, Terho Lehtimäki, Heikki A. Koistinen, Meena Kumari, Qibin Qi, Ayse Demirkan, Francesco Cucca, Allan Linneberg, Reija Männikkö, Jonathan Marten, Olli T. Raitakari, Mary F. Feitosa, Paul W. Franks, Kristine Færch, Mark I. McCarthy, Marleen H.M. de Moor, Joel N. Hirschhorn, Toomas Haller, Graff, Mariaelisa [0000-0001-6380-1735], Young, Kristin L [0000-0003-0070-6145], Winkler, Thomas W [0000-0003-0292-5421], Heard-Costa, Nancy L [0000-0001-9730-0306], Renström, Frida [0000-0001-6053-298X], Barroso, Inês [0000-0001-5800-4520], Strachan, David P [0000-0001-7854-1366], Liu, Ching-Ti [0000-0002-0703-0742], Klein, Robert J [0000-0003-3539-5391], Apollo - University of Cambridge Repository, University of Helsinki, Institute for Molecular Medicine Finland, Quantitative Genetics, Clinicum, Department of Medicine, Endokrinologian yksikkö, HUS Internal Medicine and Rehabilitation, Complex Disease Genetics, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium, Edwards, Todd L., Biological Psychology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Clinical Child and Family Studies, APH - Methodology, School of Medicine / Biomedicine, Public and occupational health, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Epidemiology, Medical Microbiology & Infectious Diseases, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Internal Medicine
Subjects: Netherlands Twin Register (NTR), Epigenomics, Male, Genome-wide association study, genome, obesity, BMI, Body Mass Index, 0302 clinical medicine, Cell Signaling, Public and Occupational Health, GENE-EXPRESSION, Adiposity, Genetics & Heredity, ADIPOCYTE DIFFERENTIATION, 1184 Genetics, developmental biology, physiology, Genomics, Functional Genomics, 3. Good health, Meta-analysis, Physical Sciences, REACTIVE PROTEIN-LEVELS, Waist Circumference, Statistics (Mathematics), Waist, Genotype, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Single-nucleotide polymorphism, Locus (genetics), BINDING PROTEIN, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genome-Wide Association Studies, Genetics, Humans, Statistical Methods, Molecular Biology, Exercise, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, Science & Technology, ASSOCIATION METAANALYSIS, Physical activity, ta1184, Biology and Life Sciences, Computational Biology, Physical Activity, 030104 developmental biology, Genetic Loci, Body mass index, Mathematics, 030217 neurology & neurosurgery, Meta-Analysis, Developmental Biology, BODY-MASS INDEX, IDENTICAL-TWINS, ACTIVITY QUESTIONNAIRES, FAT DISTRIBUTION, FOOD-INTAKE, 0301 basic medicine, Cancer Research, Medicin och hälsovetenskap, Offita, Physiology, FTO gene, Genome-wide association studies, Medical and Health Sciences, Mathematical and Statistical Techniques, Waist–hip ratio, Medicine and Health Sciences, Genetics (clinical), Public Health, Global Health, Social Medicine and Epidemiology, Physiological Parameters, Female, Genomic Signal Processing, Life Sciences & Biomedicine, Research Article, Signal Transduction, lcsh:QH426-470, Biology, Research and Analysis Methods, Hreyfing (heilsurækt), Journal Article, Erfðafræði, Genetic Predisposition to Disease, Obesity, Waist-Hip Ratio, Body Weight, Human Genetics, Cell Biology, Rannsóknir, Genome Analysis, lcsh:Genetics, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 3111 Biomedicine, Genome-Wide Association Study
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery., The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (102318; 104781, 120315, 123885, 129619, 286284, 134309, 126925, 121584, 124282, 129378, 117787, 250207, 258753, 41071, 77299, 124243, 1114194, 24300796); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la Recherche; Agency for Health Care Policy Research (HS06516); Age UK Research into Ageing Fund; Åke Wiberg Foundation; ALF/LUA Research Grant in Gothenburg; ALFEDIAM; ALK-Abello´ A/S (Hørsholm, Denmark); American Heart Association (13POST16500011, 10SDG269004); Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; AstraZeneca; Australian Associated Brewers; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); Avera Research Institute; Bayer Diagnostics; Becton Dickinson; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); Biocentrum Helsinki; Boston Obesity Nutrition Research Center (DK46200); British Heart Foundation (RG/10/12/28456, SP/04/002); Canada Foundation for Innovation; Canadian Institutes of Health Research (FRN-CCT-83028); Cancer Research UK; Cardionics; Center for Medical Systems Biology; Center of Excellence in Complex Disease Genetics and SALVECenter of Excellence in Genomics (EXCEGEN); Chief Scientist Office of the Scottish Government; City of Kuopio; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF–1333-00124, DFF–1331-007308); Danish Diabetes Academy; Danish Medical Research Council; Department of Psychology and Education of the VU University Amsterdam; Diabetes Hilfs- und Forschungsfonds Deutschland; Dutch Brain Foundation; Dutch Ministry of Justice; Emil Aaltonen Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (IUT20-60, IUT24-6); Estonian Ministry of Education and Research (3.2.0304.11-0312); European Commission (230374, 284167, 323195, 692145, FP7 EurHEALTHAgeing-277849, FP7 BBMRI-LPC 313010, nr 602633, HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, FP6 LSHM-CT-2004-005272, FP5 QLG2-CT-2002-01254, FP6 LSHG-CT-2006-01947, FP7 HEALTH-F4-2007-201413, FP7 279143, FP7 201668, FP7 305739, FP6 LSHG-CT-2006-018947, HEALTH-F4-2007-201413, QLG1-CT-2001-01252); European Regional Development Fund; European Science Foundation (EuroSTRESS project FP-006, ESF, EU/QLRT-2001-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 03IS2061A); Federal State of Mecklenburg - West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Food Standards Agency; Fondation de France; Fonds Santé; Genetic Association Information Network of the Foundation for the National Institutes of Health; German Diabetes Association; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); German Research Council (SFB-1052, SPP 1629 TO 718/2-1); GlaxoSmithKline; Göran Gustafssons Foundation; Göteborg Medical Society; Health and Safety Executive; Heart Foundation of Northern Sweden; Icelandic Heart Association; Icelandic Parliament; Imperial College Healthcare NHS Trust; INSERM, Réseaux en Santé Publique, Interactions entre les déterminants de la santé; Interreg IV Oberrhein Program (A28); Italian Ministry of Economy and Finance; Italian Ministry of Health (ICS110.1/RF97.71); John D and Catherine T MacArthur Foundation; Juho Vainio Foundation; King's College London; Kjell och Märta Beijers Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); Leiden University Medical Center; Lilly; LMUinnovativ; Lundbeck Foundation; Lundberg Foundation; Medical Research Council of Canada; MEKOS Laboratories (Denmark); Merck Santé; Mid-Atlantic Nutrition Obesity Research Center (P30 DK72488); Ministère de l’Économie, de l’Innovation et des Exportations; Ministry for Health, Welfare and Sports of the Netherlands; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science of the Netherlands; MRC Human Genetics Unit; MRC-GlaxoSmithKline Pilot Programme Grant (G0701863); Municipality of Rotterdam; Netherlands Bioinformatics Centre (2008.024); Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Genomics Initiative; Netherlands Organisation for Health Research and Development (904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192); Netherlands Organisation for Health Research and Development (2010/31471/ZONMW); Netherlands Organisation for Scientific Research (10-000-1002, GB-MW 940-38-011, 100-001-004, 60-60600-97-118, 261-98-710, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MaGW 452-04-314, GB-MaGW 452-06-004, 175.010.2003.005, 175.010.2005.011, 481-08-013, 480-05-003, 911-03-012); Neuroscience Campus Amsterdam; NHS Foundation Trust; Novartis Pharmaceuticals; Novo Nordisk; Office National Interprofessionel des Vins; Paavo Nurmi Foundation; Påhlssons Foundation; Päivikki and Sakari Sohlberg Foundation; Pierre Fabre; Republic of Croatia Ministry of Science, Education and Sport (108-1080315-0302); Research Centre for Prevention and Health, the Capital Region for Denmark; Research Institute for Diseases in the Elderly (014-93-015, RIDE2); Roche; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Executive Health Department (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du Diabète; State of Bavaria; Stroke Association; Swedish Diabetes Association; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20140543); Swedish Research Council (2015-03657); Swedish Medical Research Council (K2007-66X-20270-01-3, 2011-2354); Swedish Society for Medical Research; Swiss National Science Foundation (33CSCO-122661, 33CS30-139468, 33CS30-148401); Tampere Tuberculosis Foundation; The Marcus Borgström Foundation; The Royal Society; The Wellcome Trust (084723/Z/08/Z, 088869/B/09/Z); Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar Söderberg's Foundation; UK Department of Health; UK Diabetes Association; UK Medical Research Council (MC_U106179471, G0500539, G0600705, G0601966, G0700931, G1002319, K013351, MC_UU_12019/1); UK National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre; UK National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; UK National Institute for Health Research (RP-PG-0407-10371); Umeå University Career Development Award; United States – Israel Binational Science Foundation Grant (2011036); University Hospital Oulu (75617); University Medical Center Groningen; University of Tartu (SP1GVARENG); National Institutes of Health (AG13196, CA047988, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSC271201100004C, HHSN268200900041C, HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268201500001I, HL36310, HG002651, HL034594, HL054457, HL054481, HL071981, HL084729, HL119443, HL126024, N01-AG12100, N01-AG12109, N01-HC25195, N01-HC55015, N01-HC55016, N01-HC55018, N01-HC55019, N01-HC55020, N01-HC55021, N01-HC55022, N01-HD95159, N01-HD95160, N01-HD95161, N01-HD95162, N01-HD95163, N01-HD95164, N01-HD95165, N01-HD95166, N01-HD95167, N01-HD95168, N01-HD95169, N01-HG65403, N02-HL64278, R01-HD057194, R01-HL087641, R01-HL59367, R01HL-086694, R01-HL088451, R24-HD050924, U01-HG-004402, HHSN268200625226C, UL1-RR025005, UL1-RR025005, UL1-TR-001079, UL1-TR-00040, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, DA12854, MH081802, MH66206, R01-D004215701A, R01-DK075787, R01-DK089256, R01-DK8925601, R01-HL088451, R01-HL117078, R01-DK062370, R01-DK072193, DK091718, DK100383, DK078616, 1Z01-HG000024, HL087660, HL100245, R01DK089256, 2T32HL007055-36, U01-HL072515-06, U01-HL84756, NIA-U01AG009740, RC2-AG036495, RC4-AG039029, R03 AG046389, 263-MA-410953, 263-MD-9164, 263-MD-821336, U01-HG004802, R37CA54281, R01CA63, P01CA33619, U01-CA136792, U01-CA98758, RC2-MH089951, MH085520, R01-D0042157-01A, MH081802, 1RC2-MH089951, 1RC2-MH089995, 1RL1MH08326801, U01-HG007376, 5R01-HL08767902, 5R01MH63706:02, HG004790, N01-WH22110, U01-HG007033, UM1CA182913, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221); USDA National Institute of Food and Agriculture (2007-35205-17883); Västra Götaland Foundation; Velux Foundation; Veterans Affairs (1 IK2 BX001823); Vleugels Foundation; VU University’s Institute for Health and Care Research (EMGO+, HEALTH-F4-2007-201413) and Neuroscience Campus Amsterdam; Wellcome Trust (090532, 091551, 098051, 098381); Wissenschaftsoffensive TMO; and Yrjö Jahnsson Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2017

210. Multivariate Genome-wide and integrated transcriptome and epigenome-wide analyses of the Well-being spectrum

Author: Meike Bartels, Michel G. Nivard, Gonneke Willemsen, Abdel Abdellaoui, Yanchun Bao, Melissa C. Smart, van Dongen J, Dorret I. Boomsma, de Geus E, Jouke-Jan Hottenga, van de Weijer Mp, Rick Jansen, Meena Kumari, Hill F. Ip, and Bart M. L. Baselmans
Subjects: Genetics, 0303 health sciences, Single-nucleotide polymorphism, Epigenome, Biology, Genome, Phenotype, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Gene expression, DNA methylation, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Phenotypes related to well-being (life satisfaction, positive affect, neuroticism, and depressive symptoms), are genetically highly correlated (| rg | > .75). Multivariate genome-wide analyses (Nobs = 958,149) of these traits, collectively referred to as the well-being spectrum, reveals 63 significant independent signals, of which 29 were not previously identified. Transcriptome and epigenome analyses implicate variation in gene expression at 8 additional loci and CpG methylation at 6 additional loci in the etiology of well-being. We leverage an anatomically comprehensive survey of gene expression in the brain to annotate our findings, showing that SNPs within genes excessively expressed in the cortex and part of the hippocampal formation are enriched in their effect on well-being.
Published: 2017
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211. Novel blood pressure locus and gene discovery using GWAS and expression datasets from blood and the kidney

Author: Ganesh Chauhan, Dragana Vuckovic, Yingchang Lu, Bernard Keavney, Patricia B. Munroe, Tim D. Spector, Tamara B. Harris, Chiara Batini, Harold Snieder, Yusuf Demirkale, Ulf Gyllensten, Heather J. Cordell, Christopher Newton-Cheh, Anne-Claire Vergnaud, Christophe Tzourio, Giorgia Girotto, Morris A. Swertz, John C. Chambers, Xiuqing Guo, Caterina Barbieri, Joris Deelen, Morris Brown, Igor Rudan, Christopher P. Nelson, Paul Knekt, Antti-Pekka Sarin, Peter Vollenweider, Lynda M. Rose, Ozren Polasek, Nilesh J. Samani, Murielle Bochud, James F. Wilson, Anna Morgan, Gail Davies, Ian J. Deary, Massimiliano Cocca, Antti Jula, Ioanna Tzoulaki, Jaspal S. Kooner, Sarah H Wild, Peter S. Braund, John M. Starr, Simon Thom, Christian Gieger, Rainer Rettig, John M. C. Connell, Marina Ciullo, Jian'an Luan, Rodney J. Scott, Franco Giulianini, Brenda W.J.H. Penninx, Mika Kähönen, Alison Pattie, Nabi Shah, Weihua Zhang, Ruth J. F. Loos, Maris Laan, Martin Farrall, Rick Jansen, Albert V. Smith, Sarah E. Harris, Alex S. F. Doney, Najaf Amin, Lenore J. Launer, Paul M. Ridker, John Attia, Alanna C. Morrison, Kay-Tee Khaw, Jaume Marrugat, Hugh Watkins, David C. Liewald, Pim van der Harst, Benjamin Lehne, Jennifer E. Huffman, Meixia Ren, Zoltán Kutalik, Lars Lind, Walter Palmas, Teresa Ferreira, David J. Stott, Janina S. Ried, Bruce M. Psaty, Paul F. O'Reilly, Massimo Mangino, Tõnu Esko, Jonathan Marten, Nick Shrine, Anders Hamsten, Tineka Blake, Yuri Milaneschi, Jing Hua Zhao, David Conen, Kristin L. Ayers, Germaine C. Verwoert, Veikko Salomaa, Olli T. Raitakari, Jaakko Tuomilehto, Louise V. Wain, Jennie Hui, Elin Org, Gonçalo R. Abecasis, Vilmundur Gudnason, Andrew A. Hicks, Rossella Sorice, Borbala Mifsud, Helen R. Warren, Jerome I. Rotter, Erwin P. Bottinger, Roberto Elosua, Antonietta Robino, Ilaria Gandin, Andres Metspalu, Marjo-Riitta Järvelin, Guillaume Paré, Anne U. Jackson, Jie Yao, Kent D. Taylor, Denis C. Shields, Andrew D. Morris, Daniela Ruggiero, Samuli Ripatti, C M Lindgren, Mike A. Nalls, Erik Ingelsson, Michela Traglia, Jeffrey Damman, J. Wouter Jukema, Catharina A. Hartman, Eco J. C. de Geus, Colin N. A. Palmer, Peter J. van der Most, Neil Poulter, Robert A. Scott, Anuj Goel, Aude Saint Pierre, Annette Peters, Paul Elliott, Daniel I. Chasman, Marco Brumat, Dennis O. Mook-Kanamori, Priyanka Nandakumar, Roby Joehanes, Cornelia M. van Duijn, Joshua C. Bis, Eleftheria Zeggini, Archie Campbell, Ivana Kolcic, Terho Lehtimäki, Mattias Frånberg, David S. Siscovick, Dan E. Arking, Shih-Jen Hwang, Stella Trompet, Christopher Oldmeadow, A. Mesut Erzurumluoglu, Nicholas J. Wareham, Alice Stanton, Chrysovalanto Mamasoula, Seppo Koskinen, Uwe Völker, Albertine J. Oldehinkel, Evangelos Evangelou, Pekka Jousilahti, Dorret I. Boomsma, Harry Campbell, Peter J. Munson, Aarno Palotie, Daniela Toniolo, He Gao, Ruifang Li-Gao, Claudia Langenberg, Kati Kristiansson, Åsa Johansson, Johan Sundström, Francis S. Collins, Alan J. Gow, Caroline Hayward, Markus Perola, Renée de Mutsert, Alan James, Ben A. Oostra, Alexander Teumer, Joanne Knight, Vilmantas Giedraitis, Marty Larson, Helena Schmidt, Sébastien Thériault, Peter S. Sever, Maryam Abedi, André G. Uitterlinden, Marc A. Seelen, Georg Ehret, Cristina Menni, Anubha Mahajan, Elizabeth G. Holliday, Ilja M. Nolte, Stéphanie Debette, Paolo Gasparini, Teemu J. Niiranen, Stefan Enroth, Mark J. Caulfield, Andrew P. Morris, Aki S. Havulinna, Cinzia Sala, Peter P. Pramstaller, Marcus Dörr, Quang Tri Nguyen, Claudia P. Cabrera, Bram P. Prins, Peter K. Joshi, Sekar Kathiresan, Lorna M. Lopez, Reinhold Schmidt, Sandosh Padmanabhan, Teresa Nutile, Gonneke Willemsen, François Mach, Michael Boehnke, John Beilby, Leo-Pekka Lyytikäinen, Alan F. Wright, Edith Hofer, Siim Sõber, Ahmad Vaez, Albert Hofman, Martin H. de Borst, Oscar H. Franco, Yongmei Liu, Tatijana Zemunik, Kenneth Rice, Veronique Vitart, Aravinda Chakravarti, Jouke-Jan Hottenga, Fabiola M. Del Greco, Yasaman Saba, Daniel Levy, Li Lin, Michael R. Barnes, Rona J. Strawbridge, Harriëtte Riese, Andrew D. Johnson, David P. Strachan, and Martin D. Tobin
Subjects: Genetics, 0303 health sciences, Genomics, Locus (genetics), Genome-wide association study, Biology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Blood pressure, Genetic variation, 1000 Genomes Project, Gene, 030217 neurology & neurosurgery, Imputation (genetics), 030304 developmental biology
Abstract: Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150,134 European ancestry individuals and sought significant evidence for independent replication in a further 228,245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9 and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12,607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in BP regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
Published: 2017
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212. Heritability of lifetime ecstasy use

Author: Tibor M. Brunt, Gonneke Willemsen, Annabel Vreeker, Karin J. H. Verweij, Jorien L. Treur, Dorret I. Boomsma, Jacqueline M. Vink, Academic Medical Center, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Biological Psychology, Molecular and Cellular Neurobiology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, and APH - Methodology
Subjects: Netherlands Twin Register (NTR), Male, N-Methyl-3,4-methylenedioxyamphetamine, Ecstasy, Twins, Environment, Toxicology, Euphoriant, Developmental psychology, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Surveys and Questionnaires, medicine, Journal Article, Prevalence, Twins, Dizygotic, Humans, Pharmacology (medical), Registries, Netherlands, Pharmacology, Psychotropic Drugs, Siblings, Psychoactive drug, MDMA, Twins, Monozygotic, Heritability, Elevated mood, Twin study, 030227 psychiatry, Psychiatry and Mental health, Trait, Female, Psychology, Developmental Psychopathology, 030217 neurology & neurosurgery, medicine.drug, Demography
Abstract: Item does not contain fulltext Background: Ecstasy is a widely used psychoactive drug that users often take because they experience positive effects such as increased euphoria, sociability, elevated mood, and heightened sensations. Ecstasy use is not harmless and several immediate and long term side effects have been identified. Lifetime ecstasy use is likely to be partly influenced by genetic factors, but no twin study has determined the heritability. Here, we apply a classical twin design to a large sample of twins and siblings to estimate the heritability of lifetime ecstasy use. Methods: The sample comprised 8,500 twins and siblings aged between 18 and 45 years from 5,402 families registered at the Netherlands Twin Registry. In 2013-2014 participants filled out a questionnaire including a question whether they had ever used ecstasy. We used the classical twin design to partition the individual differences in liability to ecstasy use into that due to genetic, shared environmental, and residual components. Results: Overall, 10.4% of the sample had used ecstasy during their lifetime, with a somewhat higher prevalence in males than females. Twin modelling indicated that individual differences in liability to lifetime ecstasy use are for 74% due to genetic differences between individuals, whereas shared environmental and residual factors explain a small proportion of its liability (5% and 21%, respectively). Although heritability estimates appeared to be higher for females than males, this difference was not significant. Conclusions: Lifetime ecstasy use is a highly heritable trait, which indicates that some people are genetically more vulnerable to start using ecstasy than others. 4 p.
Published: 2017

213. Education in Twins and Their Parents Across Birth Cohorts Over 100 years : An Individual-Level Pooled Analysis of 42-Twin Cohorts

Author: Corrado Fagnani, Shandell Pahlen, Christian Kandler, Nicholas G. Martin, Ingunn Brandt, Judy L. Silberg, S. Alexandra Burt, Fazil Aliev, Chika Honda, Dorret I. Boomsma, Adam Domonkos Tarnoki, Matt McGue, William S. Kremen, Antti Latvala, Fruhling Rijsdijk, Keith E. Whitfield, Joohon Sung, Per Tynelius, José Maia, Ariel Knafo-Noam, Catarina Almqvist, Meike Bartels, Carol E. Franz, Thorkild I. A. Sørensen, Maria Antonietta Stazi, Nancy L. Pedersen, Mikio Watanabe, John L. Hopper, Karri Silventoinen, Thomas M. Mack, Zengchang Pang, Jooyeon Lee, Kimberly J. Saudino, Robert Vlietinck, Lindon J. Eaves, Athula Sumathipala, Sevgi Y. Öncel, Robert F. Krueger, Vilhelmina Ullemar, Lucía Colodro-Conde, Patrik K. E. Magnusson, K. Paige Harden, Feng Ning, Wendy Cozen, Anna K. Dahl Aslan, Grant W. Montgomery, David A. Butler, Sooji Lee, Finn Rasmussen, Sisira Siribaddana, Glen E. Duncan, Sarah E. Medland, Lior Abramson, Matthew Hotopf, Juan R. Ordoñana, David Mankuta, Fuling Ji, Kauko Heikkilä, Juan F. Sánchez-Romera, Dedra Buchwald, Dongfeng Zhang, Jina Kim, Paul Lichtenstein, Gonneke Willemsen, Hermine H. Maes, Yoon-Mi Hur, Sonia Brescianini, Tessa L. Cutler, Catherine Derom, Yoshie Yokoyama, Thomas Sevenius Nilsen, Qihua Tan, Eric Turkheimer, Hoe-Uk Jeong, Robin P. Corley, Clare H. Llewellyn, Yoshinori Iwatani, Jennifer R. Harris, Laura A. Baker, Elliot M. Tucker-Drob, Richard J. Rose, Duarte L. Freitas, Aline Jelenkovic, Amie E. Hwang, Jack Goldberg, Fujio Inui, Andreas Busjahn, Ruth J. F. Loos, Kelly L. Klump, Tracy L. Nelson, David Laszlo Tarnoki, Catherine Tuvblad, Jaakko Kaprio, Reijo Sund, Brooke M. Huibregtse, Margaret Gatz, Catharina E. M. van Beijsterveldt, Markku Koskenvuo, Abigail Fisher, Esther Rebato, Michael J. Lyons, Department of Social Research (2010-2017), Sociology, Center for Population, Health and Society, Institute for Molecular Medicine Finland, Clinicum, Department of Public Health, University of Helsinki, Markku Koskenvuo / Principal Investigator, Population Research Unit (PRU), Genetic Epidemiology, Biological Psychology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, and Kırıkkale Üniversitesi
Subjects: Male, Netherlands Twin Register (NTR), Twins, INTELLIGENCE, SWEDISH MEN, Cohort Studies, 0302 clinical medicine, HEIGHT, Parental education, 3123 Gynaecology and paediatrics, Twins, Dizygotic, 030212 general & internal medicine, Genetics (clinical), BODY-SIZE, education, Academic Success, 030219 obstetrics & reproductive medicine, parental education, Obstetrics and Gynecology, Zygosity, Public Health, Global Health, Social Medicine and Epidemiology, twins, ASSOCIATION, zygosity, 3142 Public health care science, environmental and occupational health, Pooled analysis, Female, Birth cohort, Twins Early Development Study, SDG 4 - Quality Education, Cohort study, COUNTRIES, GENETICS, Biology, Article, 03 medical and health sciences, AGE, Journal Article, Humans, Models, Genetic, Twins, Monozygotic, Individual level, Twin study, COGNITIVE-ABILITY, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Socioeconomic Factors, Faculdade de Ciências Sociais, CODATWINS PROJECT, Pediatrics, Perinatology and Child Health, Demography
Abstract: Sund, Reijo/0000-0002-6268-8117; Heikkila, Kauko/0000-0002-9256-8028; Knafo-Noam, Ariel/0000-0003-0613-1960; Montgomery, Grant W/0000-0002-4140-8139; de Freitas, Duarte Luis/0000-0001-6642-3370; ONCEL, Sevgi YURT/0000-0002-0990-292X; Fagnani, Corrado/0000-0001-5771-7772; Loos, Ruth J F/0000-0002-8532-5087; Kaprio, Jaakko/0000-0002-3716-2455; Huibregtse, Brooke M./0000-0003-0977-7249; ROMERA, JUAN FRANCISCO SANCHEZ/0000-0002-5405-6216; Colodro-Conde, Lucia/0000-0002-9004-364X; Tan, Qihua/0000-0003-3194-0030; Ordonana, Juan R./0000-0001-7779-6017; Kandler, Christian/0000-0002-9175-235X; Aliev, Fazil/0000-0001-8357-4699; Siribaddana, Sisira/0000-0001-5821-2557; Busjahn, Andreas/0000-0001-9650-6919; Tan, Qihua/0000-0003-3194-0030; Rasmussen, Finn/0000-0001-7915-7809; Silventoinen, Karri/0000-0003-1759-3079; Pedersen, Nancy/0000-0001-8057-3543; van Beijsterveldt, Toos/0000-0002-6617-4201; Franz, Carol/0000-0002-8987-1755; Rebato, Esther/0000-0003-1221-8501; Pahlen, Shandell/0000-0003-0753-4155; Harden, Kathryn/0000-0002-1557-6737; Bartels, Meike/0000-0002-9667-7555; Willemsen, Gonneke/0000-0003-3755-0236; Latvala, Antti/0000-0001-5695-117X WOS: 000412597600005 PubMed: 28975875 Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected. CODATwins project (Academy of Finland) [266592]; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 HD068435, R01 MH062375, 1R01ESO15150-01, R21 AG039572, AA023322, HD081437, NIA R01 AG018384, R01 AG018386, R01 AG022381, R01 AG022982]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; National Institute on AgingUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1RO1-AG13662-01A2]; Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF)Stockholm County Council; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study [HD10333]; Fund of Scientific Research, Flanders and Twins; ENGAGE European Network for Genetic and Genomic Epidemiology [201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 263278, 264146]; Cancer Research UKCancer Research UK [C1418/A7974]; Medexpert Ltd., Budapest, Hungary; Global Research Network Program of the National Research Foundation [NRF 2011-220-E00006]; European Research Council (ERC)European Research Council (ERC) [240994]; Michigan State University; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01]; Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) [R01-HD066040]; MSU Foundation [11-SPG-2518]; Fundacion SenecaFundacion Seneca; Regional Agency for Science and Technology, Murcia, Spain [08633/PHCS/08, 15302/PHCS/10, 19479/PI/14]; Ministry of Science and Innovation, SpainSpanish Government [PSI2009-11560, PSI2014-56680-R]; MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192]; VU University's Institute for Health and Care Research (EMGO+); European Research CouncilEuropean Research Council (ERC) [ERC - 230374]; Avera Institute, Sioux Falls, South Dakota (USA); National Research Foundation of KoreaNational Research Foundation of Korea [NRF-371-2011-1 B00047]; Krkkale University Research Grant [2009/43]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Cooperative Studies Program of the Office of Research AMP; Development of the United States Department of Veterans Affairs; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH58354]; JSPS KAKENHI JP [23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261]; [5T32DA017637-11]; [POCI/DES/56834/2004]; [NIH RC2 HL103416] This study was conducted within the CODATwins project (Academy of Finland #266592). The Australian Twin Registry is supported by a Centre of Research Excellence (grant ID 1079102) from the National Health and Medical Research Council administered by the University of Melbourne. The Boston University Twin Project is funded by grants (#R01 HD068435 #R01 MH062375) from the National Institutes of Health to K. Saudino. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. The CATSS-Study is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants provided by the Stockholm County Council (ALF-projects), the Swedish Heart-Lung Foundation and the Swedish Asthma and Allergy Association's Research Foundation. Colorado Twin Registry is funded by NIDA funded center grant DA011015 and Longitudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637-11. Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (grant numbers: 213506, 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 263278, and 264146 to J Kaprio). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Longitudinal Israeli Study of Twins was funded by the Starting Grant no. 240994 from the European Research Council (ERC) to Ariel Knafo. The Michigan State University Twin Registry has been supported by Michigan State University, as well as grants R01-MH081813, R01-MH0820-54, R01-MH092377-02, R21-MH070542-01, R03-MH63851-01 from the National Institute of Mental Health (NIMH), R01-HD066040 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD), and 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the NICHD, or the National Institutes of Health. The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572.; r Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC - 230374), the Avera Institute, Sioux Falls, South Dakota (USA). Madeira data comes from the following project: Genetic and environmental influences on physical activity, fitness, and health: the Madeira family study. Project reference: POCI/DES/56834/2004. Founded by the Portuguese agency for research (The Foundation for Science and Technology [FCT]). South Korea Twin Registry is supported by National Research Foundation of Korea (NRF-371-2011-1 B00047). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from the National Institutes of Health. S. Y. oncel and F. Aliev are supported by Krkkale University Research Grant: KKU, 2009/43 and TUBITAK grant 114C117. Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The West Japan Twins and Higher Order Multiple Births Registry was supported by Grant-in-Aid for Scientific Research (B) (grant number 15H05105) from the Japan Society for the Promotion of Science. The University of Southern California Twin Study is funded by a grant from the National Institute of Mental Health (R01 MH58354). Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261).
Published: 2017

214. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: P. Eline Slagboom, Massimo Mangino, David J. Porteous, Karin Leander, Nancy L. Heard-Costa, Sharon L.R. Kardia, Jennifer Bragg, Ken K. Ong, Igor Rudan, Blair H. Smith, Mark A. Sarzynski, Torben Hansen, James F. Wilson, Weihua Zhang, Zoltán Kutalik, Karl Gertow, Yii-Der Ida Chen, Daniele Cusi, Lu Qi, Nicholas G. Martin, Peter Vollenweider, Thomas W. Winkler, Graciela E. Delgado, Thorkild I. A. Sørensen, André G. Uitterlinden, J. Wouter Jukema, Rajesh Rawal, Dena G. Hernandez, Amy J. Swift, Naveed Sattar, Ruth J. F. Loos, George Dedoussis, Ani Manichaikul, Henrik Vestergaard, Jian'an Luan, Luting Xue, Charles Kooperberg, Rona J. Strawbridge, John-Olov Jansson, Jian Gong, Martina Müller-Nurasyid, L. Adrienne Cupples, Frida Renström, Stephan J. L. Bakker, Ivana Kolcic, Mathias Gorski, Tamara B. Harris, Sandosh Padmanabhan, Stephanie A. Bien, Arthur W. Musk, Cristina Menni, Steve Buyske, Anubha Mahajan, Claudia Schurmann, John Blangero, Natalia Pervjakova, Inês Barroso, Kristin L. Young, Momoko Horikoshi, Robert A. Scott, Ozren Polasek, Shafqat Ahmad, Jeremiah Perez, Stella Trompet, Claude Bouchard, Claudia Langenberg, Paul M. Ridker, Tuomas O. Kilpeläinen, Oddgeir L. Holmen, Tarunveer S. Ahluwalia, Alan F. Wright, Ulf de Faire, Cecilia M. Lindgren, Misa Graff, Jie Huang, Liesbeth Vandenput, Marcel Bruinenberg, Luigi Ferrucci, Johanne Marie Justesen, Audrey Y. Chu, Melanie Waldenberger, Karen L. Mohlke, Ching-Ti Liu, Barbara Thorand, Joseph Hung, Pim van der Harst, Colin A. McKenzie, Sailaja Vedantam, Gitta H. Lubke, Bruna Gigante, Göran Hallmans, Sara Lupoli, Anja Ludolph-Donislawski, Michael Boehnke, Treva Rice, Lori L. Bonnycastle, Daniele Braga, Mika Kähönen, Joel Eriksson, Gonçalo R. Abecasis, Joseph M. Wu, Niels Grarup, Ilja M. Nolte, Jonathan Marchini, Georg Homuth, Pamela A. F. Madden, John Beilby, Andrew D. Johnson, Nanette R. Lee, Caroline Hayward, Unhee Lim, Bamidele O. Tayo, Peter S. Chines, Lynda M. Rose, Amélie Bonnefond, Elena Tremoli, Serena Sanna, David P. Strachan, Barbara McKnight, Narisu Narisu, Anton J. M. de Craen, David R. Weir, Albertine J. Oldehinkel, Jessica Tyrrell, Beverley Balkau, Kirsti Kvaløy, Marie-Claude Vohl, Jennifer A. Smith, Rainer Rauramaa, Andrew C. Heath, Erwin P. Bottinger, Andrew Wong, Günther Silbernagel, Mattias Lorentzon, Philippe Froguel, Uzma Afzal, Tanja B. Grammer, Dabeeru C. Rao, Charlotta Pisinger, Nicola Glorioso, Najaf Amin, Andrew P. Morris, Tanguy Corre, Alan James, Julius S. Ngwa, Jennifer E. Huffman, Gudny Eiriksdottir, Maija Hassinen, Lenore J. Launer, Marit E. Jørgensen, Dorret I. Boomsma, Harry Campbell, Scott Coggeshall, Timothy M. Frayling, Konstantin Strauch, Johanna Kuusisto, David Hadley, Penny Gordon-Larsen, Xuan Deng, Dorothée Thuillier, Albert V. Smith, Jaakko Tuomilehto, Harald Grallert, Lynne J. Hocking, Dan Mellström, M. Carola Zillikens, Lars Lind, Hester M. den Ruijter, Gemma Cadby, Joanne E. Curran, Richard N. Bergman, David J. Stott, Matthias Olden, Veronique Vitart, Robert Luben, Cinzia Sarti, Gert J. de Borst, Lyle J. Palmer, Sven Bergmann, Alexander Teumer, John D. Eicher, Marcus E. Kleber, Marie Loh, Genovefa Kolovou, Iris M. Heid, Gonneke Willemsen, Marie Neergaard Harder, David J. Hunter, Stefania Bandinelli, Francis S. Collins, Hans J. Grabe, Virginia Fisher, John Whitfield, Leo-Pekka Lyytikäinen, Salome Scholtens, Tamuno Alfred, Richard S. Cooper, Jouke-Jan Hottenga, Martina Chittani, Jan A. Staessen, Bernhard K. Krämer, Markku Laakso, Min A. Jhun, Marjo-Riitta Järvelin, Saima Afaq, Rita P. S. Middelberg, Jing Hua Zhao, Toshiko Tanaka, Kent D. Taylor, Rudi G. J. Westendorp, Panagiotis Deloukas, Nina Hutri-Kähönen, Reiner Biffar, Krista Fischer, Leena Kinnunen, Diana Kuh, Jaspal S. Kooner, Caroline S. Fox, Harold Snieder, Pau Navarro, Stéphane Lobbens, Tao Huang, Vilmundur Gudnason, Jacqueline M. Vink, Terrence Forrester, Kari E. North, Annette Peters, Mika Kivimäki, David Schlessinger, Ian Ford, Kristian Hveem, Christopher A. Haiman, Lucia A. Hindorff, Oluf Pedersen, Ingrid B. Borecki, Bruce H. R. Wolffenbuttel, Nicholas J. Wareham, Cornelia M. van Duijn, Lawrence F. Bielak, Loic Le Marchand, Linda S. Adair, Tõnu Esko, Anne U. Jackson, Ying Wu, Eco J. C. de Geus, Jana V. van Vliet-Ostaptchouk, Louis Pérusse, Peter J. van der Most, Ulrike Peters, Magnus Karlsson, Anders Hamsten, Anne E. Justice, Alena Stančáková, Henning Tiemeier, Eric Boerwinkle, Catharina A. Hartman, Claes Ohlsson, Grant W. Montgomery, Elise Lim, Traci M. Bartz, Erik Ingelsson, Martina E. Zimmermann, Laura J. Rasmussen-Torvik, Terho Lehtimäki, Heikki A. Koistinen, Pirjo Komulainen, Damiano Baldassarre, Marten A. Siemelink, Niek Verweij, Gerard Pasterkamp, Markus Juonala, Wei Zhao, Andres Metspalu, Sander W. van der Laan, Tuomo Rankinen, Timo A. Lakka, Yun Ju Sung, Heather M. Stringham, Bruce M. Psaty, Niha Zubair, Stavroula Kanoni, Saskia Haitjema, Bengt Sennblad, Llilda Barata, Morris A. Swertz, Mary F. Feitosa, Tim D. Spector, Paul W. Franks, Qibin Qi, Francesco Cucca, Allan Linneberg, Reija Männikkö, Jonathan Marten, Olli T. Raitakari, Mark I. McCarthy, Joel N. Hirschhorn, Winfried März, Sarah H. Wild, Meena Kumari, Nese Direk, Patricia A. Peyser, Jessica D. Faul, John C. Chambers, Nicholas D. Hastie, Mette Hollensted, Jacek Czajkowski, Daniel I. Chasman, Matthias Nauck, Gérard Waeber, Brendan M. Buckley, Kai Savonen, Judith M. Vonk, Carsten A. Böger, Loic Yengo, Anna Eriksson, Henry Völzke, Pedro Marques-Vidal, Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Cardiovascular Centre (CVC), Clinicum, Department of Medicine, University of Helsinki, Endokrinologian yksikkö, HUS Internal Medicine and Rehabilitation, Luan, Jian'an [0000-0003-3137-6337], Marten, Jonathan [0000-0001-6916-2014], Langenberg, Claudia [0000-0002-5017-7344], Luben, Robert [0000-0002-5088-6343], Ong, Kenneth [0000-0003-4689-7530], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Personalized Medicine, Epidemiology, Erasmus MC other, Medical Microbiology & Infectious Diseases, Internal Medicine, Child and Adolescent Psychiatry / Psychology, and Psychiatry
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Medicin och hälsovetenskap, Offita, Chemistry(all), Epidemiology, General Physics and Astronomy, Genome-wide association study, methods [Genome-Wide Association Study], Biochemistry, Genome-wide association studies, Medical and Health Sciences, Body Mass Index, genetics [Obesity], Genetics research, IMPUTATION, Body Fat Distribution, genetics [Genetic Predisposition to Disease], OXIDATIVE STRESS, POPULATION, Adiposity, METABOLIC SYNDROME, Genetics, education.field_of_study, Multidisciplinary, Smoking, Public Health, Global Health, Social Medicine and Epidemiology, genetics [Smoking], ASSOCIATION, 3142 Public health care science, environmental and occupational health, 3. Good health, Multidisciplinary Sciences, DEFICIENCY, Phenotype, ADDICTION, Science & Technology - Other Topics, Medical genetics, ddc:500, Waist Circumference, Reykingar, genetics [Adiposity], Adult, medicine.medical_specialty, Science, Quantitative Trait Loci, Population, genetics [Waist Circumference], Accounting, Biology, Quantitative trait locus, Physics and Astronomy(all), Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, GWAS, obesity, smoking, MD Multidisciplinary, Genetic predisposition, medicine, Journal Article, Erfðafræði, Humans, Genetic Predisposition to Disease, Obesity, education, Genetic association, Science & Technology, VITAMIN-C, genetics [Quantitative Trait Loci], Waist-Hip Ratio, business.industry, Biochemistry, Genetics and Molecular Biology(all), Epistasis, Genetic, Rannsóknir, General Chemistry, ta3121, R1, GENE, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MICE, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, business, Body mass index, Developmental Psychopathology, Imputation (genetics), Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution., A full list of acknowledgments appears in the Supplementary Note 4. Co-author A.J.M.d.C. recently passed away while this work was in process. This work was performed under the auspices of the Genetic Investigation of ANthropometric Traits (GIANT) consortium. We acknowledge the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium for encouraging CHARGE studies to participate in this effort and for the contributions of CHARGE members to the analyses conducted for this research. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (41071, 77299, 102318, 110413, 117787, 121584, 123885, 124243, 124282, 126925, 129378, 134309, 286284); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la 359 Recherche; Agency for Health Care Policy Research (HS06516); ALF/LUA research grant in Gothenburg; ALFEDIAM; ALK-Abelló A/S; Althingi; American Heart Association (13POST16500011); Amgen; Andrea and Charles Bronfman Philanthropies; Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; Australian National Health and Medical Research Council (241944, 339462, 389875, 389891, 389892, 389927, 389938, 442915, 442981, 496739, 552485, 552498); Avera Institute; Bayer Diagnostics; Becton Dickinson; BHF (RG/14/5/30893); Boston Obesity Nutrition Research Center (DK46200), Bristol-Myers Squibb; British Heart Foundation (RG/10/12/28456, RG2008/08, RG2008/014, SP/04/002); Medical Research Council of Canada; Canadian Institutes for Health Research (FRCN-CCT-83028); Cancer Research UK; Cardionics; Cavadis B.V., Center for Medical Systems Biology; Center of Excellence in Genomics; CFI; CIHR; City of Kuopio; CNAMTS; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF-1333-00124, DFF-1331-00730B); County Council of Dalarna; Dalarna University; Danish Council for Strategic Research; Danish Diabetes Academy; Danish Medical Research Council; Department of Health, UK; Development Fund from the University of Tartu (SP1GVARENG); Diabetes Hilfs- und Forschungsfonds Deutschland; Diabetes UK; Diabetes Research and Wellness Foundation Fellowship; Donald W. Reynolds Foundation; Dr Robert Pfleger-Stiftung; Dutch Brain Foundation; Dutch Diabetes Research Foundation; Dutch Inter University Cardiology Institute; Dutch Kidney Foundation (E033); Dutch Ministry of Justice; the DynaHEALTH action No. 633595, Economic Structure Enhancing Fund of the Dutch Government; Else Kröner-Fresenius-Stiftung (2012_A147, P48/08//A11/08); Emil Aaltonen Foundation; Erasmus University Medical Center Rotterdam; Erasmus MC and Erasmus University Rotterdam; the Municipality of Rotterdam; Estonian Government (IUT20-60, IUT24-6); Estonian Research Roadmap through the Estonian Ministry of Education and Research (3.2.0304.11-0312); European Research Council (ERC Starting Grant and 323195:SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC); European Regional Development Fund; European Science Foundation (EU/QLRT-2001-01254); European Commission (018947, 018996, 201668, 223004, 230374, 279143, 284167, 305739, BBMRI-LPC-313010, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-2011-278913, HEALTH-2011-294713-EPLORE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2013-601456, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550-HYPERGENES, HEALTH-F7-305507 HOMAGE, IMI/115006, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2004-005272, LSHM-CT-2006-037697, LSHM-CT-2007-037273, QLG1-CT-2002-00896, QLG2-CT-2002-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ0103, 01ZZ0403, 01ZZ9603, 03IS2061A, 03ZIK012); Federal State of Mecklenburg-West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Fondation Leducq; Food Standards Agency; Foundation for Strategic Research; French Ministry of Research; FRSQ; Genetic Association Information Network (GAIN) of the Foundation for the NIH; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); GlaxoSmithKline; Greek General Secretary of Research and Technology; Göteborg Medical Society; Health and Safety Executive; Healthcare NHS Trust; Healthway; Western Australia; Heart Foundation of Northern Sweden; Helmholtz Zentrum München—German Research Center for Environmental Health; Hjartavernd; Ingrid Thurings Foundation; INSERM; InterOmics (PB05 MIUR-CNR); INTERREG IV Oberrhein Program (A28); Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001); Italian Ministry of Health (ICS110.1/RF97.71); Italian Ministry of Economy and Finance (FaReBio di Qualità); Marianne and Marcus Wallenberg Foundation; the Ministry of Health, Welfare and Sports, the Netherlands; J.D.E. and Catherine T, MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; KfH Stiftung Präventivmedizin e.V.; King's College London; Knut and Alice Wallenberg Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); La Fondation de France; Leenaards Foundation; Lilly; LMUinnovativ; Lundberg Foundation; Magnus Bergvall Foundation; MDEIE; Medical Research Council UK (G0000934, G0601966, G0700931, MC_U106179471, MC_UU_12019/1); MEKOS Laboratories; Merck Santé; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs of Mecklenburg-West Pomerania; Ministry of Economic Affairs, The Netherlands; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport in the Republic of Croatia (108-1080315-0302); MRC centre for Causal Analyses in Translational Epidemiology; MRC Human Genetics Unit; MRC-GlaxoSmithKline pilot programme (G0701863); MSD Stipend Diabetes; National Institute for Health Research; Netherlands Brain Foundation (F2013(1)-28); Netherlands CardioVascular Research Initiative (CVON2011-19); Netherlands Genomics Initiative (050-060-810); Netherlands Heart Foundation (2001 D 032, NHS2010B280); Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) (56-464-14192, 60-60600-97-118, 100-001-004, 261-98-710, 400-05-717, 480-04-004, 480-05-003, 481-08-013, 904-61-090, 904-61-193, 911-11-025, 985-10-002, Addiction-31160008, BBMRI–NL 184.021.007, GB-MaGW 452-04-314, GB-MaGW 452-06-004, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MW 940-38-011, Middelgroot-911-09-032, NBIC/BioAssist/RK 2008.024, Spinozapremie 175.010.2003.005, 175.010.2007.006); Neuroscience Campus Amsterdam; NHS Foundation Trust; National Institutes of Health (1RC2MH089951, 1Z01HG000024, 24152, 263MD9164, 263MD821336, 2R01LM010098, 32100-2, 32122, 32108, 5K99HL130580-02, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, AG13196, CA047988, DA12854, DK56350, DK063491, DK078150, DK091718, DK100383, DK078616, ES10126, HG004790, HHSN268200625226C, HHSN268200800007C, HHSN268201200036C, HHSN268201500001I, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, HL043851, HL45670, HL080467, HL085144, HL087660, HL054457, HL119443, HL118305, HL071981, HL034594, HL126024, HL130114, KL2TR001109, MH66206, MH081802, N01AG12100, N01HC55015, N01HC55016, N01C55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, N01HG65403, N01WH22110, N02HL6‐4278, N01-HC-25195, P01CA33619, R01HD057194, R01HD057194, R01AG023629, R01CA63, R01D004215701A, R01DK075787, R01DK062370, R01DK072193, R01DK075787, R01DK089256, R01HL53353, R01HL59367, R01HL086694, R01HL087641, R01HL087652, R01HL103612, R01HL105756, R01HL117078, R01HL120393, R03 AG046389, R37CA54281, RC2AG036495, RC4AG039029, RPPG040710371, RR20649, TW008288, TW05596, U01AG009740, U01CA98758, U01CA136792, U01DK062418, U01HG004402, U01HG004802, U01HG007376, U01HL080295, UL1RR025005, UL1TR000040, UL1TR000124, UL1TR001079, 2T32HL007055-36, T32GM074905, HG002651, HL084729, N01-HC-25195, UM1CA182913); NIH, National Institute on Aging (Intramural funding, NO1-AG-1-2109); Northern Netherlands Collaboration of Provinces; Novartis Pharma; Novo Nordisk; Novo Nordisk Foundation; Nutricia Research Foundation (2016-T1); ONIVINS; Parnassia Bavo group; Pierre Fabre; Province of Groningen; Päivikki and Sakari Sohlberg Foundation; Påhlssons Foundation; Paavo Nurmi Foundation; Radboud Medical Center Nijmegen; Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Institute for Diseases in the Elderly; Research into Ageing; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Roche; Royal Society; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Government Health Directorates, Chief Scientist Office (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du 358 Diabète; State of Bavaria; Stiftelsen för Gamla Tjänarinnor; Stockholm County Council (560183, 592229); Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Stroke Association; Swedish Diabetes Association; Swedish Diabetes Foundation (2013-024); Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20120197, 20150711); Swedish Research Council (0593, 8691, 2012-1397, 2012-1727, and 2012-2215); Swedish Society for Medical Research; Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 31003A-143914, 33CSCO-122661, 33CS30-139468, 33CS30-148401, 51RTP0_151019); Tampere Tuberculosis Foundation; Technology Foundation STW (11679); The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community (G.0880.13, G.0881.13); The Great Wine Estates of the Margaret River Region of Western Australia; Timber Merchant Vilhelm Bangs Foundation; Topcon; Tore Nilsson Foundation; Torsten and Ragnar Söderberg's Foundation; United States – Israel Binational Science Foundation (Grant 2011036), Umeå University; University Hospital of Regensburg; University of Groningen; University Medical Center Groningen; University of Michigan; University of Utrecht; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) (b2011036); Velux Foundation; VU University’s Institute for Health and Care Research; Västra Götaland Foundation; Wellcome Trust (068545, 076113, 079895, 084723, 088869, WT064890, WT086596, WT098017, WT090532, WT098051, 098381); Wissenschaftsoffensive TMO; Yrjö Jahnsson Foundation; and Åke Wiberg Foundation. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute (NHLBI); the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services.
Published: 2017

215. Hypodopaminergic polygenic risk for polysubstance use

Author: Sabine Spijker, Rutger C. M. E. Engels, Karin J. H. Verweij, Gonneke Willemsen, Jacqueline M. Vink, Eco J. C. de Geus, Judith R. Homberg, Roy Otten, Jouke-Jan Hottenga, Joëlle A. Pasman, and Jorien L. Treur
Subjects: Genetics, Variable number tandem repeat, Framingham Risk Score, Polysubstance dependence, Genetic model, Single-nucleotide polymorphism, Heritability, Psychology, Twin study, Demography, Genetic association
Abstract: Twin studies have shown substantial heritability for polysubstance use. Previous research has sought to pinpoint this genetic influence to variants in genes related to dopamine signaling, that are known to lower baseline dopamine levels (hypodopaminergic function). Candidategene studies often used single-gene designs and have yielded inconsistent results. Genome-wide association studies mainly include Single Nucleotide Polymorphisms (SNPs). In this study, a risk score was calculated based on both SNPs as well as Variable Number of Tandem Repeats (VNTRs). Survey data on nicotine, alcohol and cannabis use from two family samples were analysed (N=2435 and N=1173). Moderate and problematic polysubstance uses were explored. A polygenic risk score was calculated by averaging the number of hypodopaminergic variants in three polymorphisms. Polysubstance use was regressed on this score with sex and age as covariates. Power was sufficient to detect small effect sizes (R2=0.4-0.8%). The hypodopaminergic polygenic risk score (HPRS) was not related to polysubstance use in either sample. There were some indications for opposing effects of individual polymorphisms and separate substance use outcomes and for an interaction of the polygenic risk score with education level. There were no effects of a score extended with extra polymorphisms, and there were no quadratic effects of the HPRS. The HPRS did not predict polysubstance use. Several explanations for these findings were ruled out. Future research might employ more comprehensive genetic models, thereby including geneenvironment interaction.
Published: 2017

216. Relative Telomere Repeat Mass in Buccal and Leukocyte-Derived DNA

Author: Conor V. Dolan, Veryan Codd, Gareth E. Davies, Erik A. Ehli, Casey T. Finnicum, Dorret I. Boomsma, Jeffrey J. Beck, Zachary M. Weber, Jason L. Petersen, Gonneke Willemsen, Biological Psychology, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, and APH - Health Behaviors & Chronic Diseases
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), Physiology, Buccal swab, Twins, lcsh:Medicine, Biochemistry, chemistry.chemical_compound, White Blood Cells, 0302 clinical medicine, Animal Cells, Nucleic Acids, Twins, Dizygotic, Medicine and Health Sciences, lcsh:Science, Child, Telomere Length, Genetics, Multidisciplinary, Covariance, Chromosome Biology, Age Factors, Hematology, Middle Aged, Reference Standards, Telomere, Body Fluids, Phenotypes, Real-time polymerase chain reaction, Telomeres, Blood, Physical Sciences, Female, Sample collection, Anatomy, Cellular Types, Blood drawing, Research Article, Adult, Chromosome Structure and Function, Adolescent, Immune Cells, Immunology, Biology, Real-Time Polymerase Chain Reaction, Chromosomes, 03 medical and health sciences, Sex Factors, SDG 3 - Good Health and Well-being, Journal Article, Humans, Aged, DNA Primers, Blood Cells, Siblings, lcsh:R, Mouth Mucosa, Biology and Life Sciences, Random Variables, Buccal administration, DNA, Twins, Monozygotic, Cell Biology, Probability Theory, DNA extraction, Molecular biology, 030104 developmental biology, chemistry, Leukocytes, Mononuclear, lcsh:Q, K562 Cells, 030217 neurology & neurosurgery, Mathematics, Developmental Biology
Abstract: Telomere length has garnered interest due to the potential role it may play as a biomarker for the cellular aging process. Telomere measurements obtained from blood-derived DNA are often used in epidemiological studies. However, the invasive nature of blood draws severely limits sample collection, particularly with children. Buccal cells are commonly sampled for DNA isolation and thus may present a non-invasive alternative for telomere measurement. Buccal and leukocyte derived DNA obtained from samples collected at the same time period were analyzed for telomere repeat mass (TRM). TRM was measured in buccal-derived DNA samples from individuals for whom previous TRM data from blood samples existed. TRM measurement was performed by qPCR and was normalized to the single copy 36B4 gene relative to a reference DNA sample (K562). Correlations between TRM from blood and buccal DNA were obtained and also between the same blood DNA samples measured in separate laboratories. Using the classical twin design, TRM heritability was estimated (N = 1892, MZ = 1044, DZ = 775). Buccal samples measured for TRM showed a significant correlation with the blood-1 (R = 0.39, p < 0.01) and blood-2 (R = 0.36, p < 0.01) samples. Sex and age effects were observed within the buccal samples as is the norm within blood-derived DNA. The buccal, blood-1, and blood-2 measurements generated heritability estimates of 23.3%, 47.6% and 22.2%, respectively. Buccal derived DNA provides a valid source for the determination of TRM, paving the way for non-invasive projects, such as longitudinal studies in children.
Published: 2017

217. Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia

Author: Stephan Ripke, A. Di Florio, Gustavo Turecki, N Bass, Ian Jones, Laura J. Scott, Lisa Hall, Martin Hautzinger, Tracy Air, Sarah Knott, Marcella Rietschel, Christel M. Middeldorp, Patrick J. Brennan, John Strauss, Nicholas G. Martin, Bertram Müller-Myhsok, Tony Davis, Andreas Reif, Katherine Gordon-Smith, Céline S. Reinbold, Urs Heilbronner, Anders Juréus, Stefan Kloiber, Andrew McQuillin, Dan Rujescu, N. Dahmen, Fermin Mayoral-Cleries, Richard M. Myers, Abdel Abdellaoui, Franck Bellivier, Gunnar Morken, Sarah E. Bergen, Manolis Kogevinas, Dorret I. Boomsma, Thomas G. Schulze, Arian Mobascher, Stefanie Heilmann-Heimbach, Sascha B. Fischer, Christine Fraser, Y. Milaneschi, Michael Conlon O'Donovan, Susan L. McElroy, Klaus Lieb, B.W.J.H. Penninx, Helmut Vedder, Fabian Streit, Piotr M. Czerski, Swapnil Awasthi, Lilijana Oruc, Caroline M. Nievergelt, Michael Bauer, Jana Strohmaier, Qingqin S. Li, Bernhard T. Baune, Roel A. Ophoff, S. E. Medland, Marco P. Boks, Gulja Babadjanova, Mark A. Frye, Christian Schmahl, M. M. Nöthen, Nicholas John Craddock, John B. Vincent, Douglas Blackwood, Marion Leboyer, Franziska Degenhardt, C. E. Schwarze, Henriette N. Buttenschøn, Tiffany A. Greenwood, Ole A. Andreassen, Toni-Kim Clarke, Loes M. Olde Loohuis, Scott D. Gordon, Björn H. Schott, Stephanie H. Witt, Stefan Roepke, John I. Nurnberger, S Van der Auwera, Lisa Jones, James D. McKay, André Tadić, Mikael Landén, Guy A. Rouleau, Monika Budde, Grant C.B. Sinnamon, Enda M. Byrne, Bruno Etain, Darja Schendel, Andreas J. Forstner, Cristiana Cruceanu, Srdjan Djurovic, Sara A. Paciga, Ney Alliey-Rodriguez, Joanna Hauser, Enrico Domenici, Peter Hoffmann, Elaine K. Green, Stéphane Jamain, Markus Schwarz, Marian L. Hamshere, Christian Witt, E.J.C. de Geus, Andrew M. McIntosh, Sven Cichon, Ole Mors, Jolanta Lissowska, Josef Frank, Pablo Cervantes, G. Kirov, Howard J. Edenberg, Ina Giegling, Grant W. Montgomery, Lydie Dietl, Martin Preisig, M. J. Owen, Martin Alda, David Curtis, Eli A. Stahl, Gonneke Willemsen, Udo Dannlowski, Rolf Adolfsson, Janice M. Fullerton, Jose Guzman-Parra, Elliot S. Gershon, Peter Holmans, Hans-Jörgen Grabe, Hualin S. Xi, Jens Treutlein, Fabio Rivas, James B. Potash, Martin Bohus, Naomi R. Wray, René S. Kahn, Katrin Gade, Sarah Kittel-Schneider, Anders D. Børglum, Susanne Lucae, Jouke-Jan Hottenga, Joanna M. Biernacka, Liz Forty, Margitta Borrmann-Hassenbach, Martin Jungkunz, Andrea Pfennig, Jutta Kammerer-Ciernioch, Maria Grigoroiu-Serbanescu, Peter R. Schofield, Stefan Herms, Amy Perry, Shashi Hitturlingappa, Markus Leber, Thomas W. Mühleisen, Philip B. Mitchell, Andrew Bethell, Huda Akil, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, Environmental Policy Analysis, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Duchange, Nathalie
Subjects: Netherlands Twin Register (NTR), Male, Linkage disequilibrium, Multifactorial Inheritance, Bipolar Disorder, FEATURES, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Genome-wide association study, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, MESH: Genotype, 0302 clinical medicine, Borderline Personality Disorder, MESH: Bipolar Disorder, Borderline personality disorder, Genetics, RISK, Psychiatry, MESH: Aged, MESH: Middle Aged, PSYCHOPATHOLOGY, MESH: Genetic Predisposition to Disease, Middle Aged, MESH: Case-Control Studies, 3. Good health, FAMILY, Psychiatry and Mental health, Schizophrenia, MESH: Young Adult, Female, Original Article, medicine.symptom, Psychology, SET, TRAITS, Adolescent, Adult, Aged, Bipolar Disorder/genetics, Borderline Personality Disorder/genetics, Case-Control Studies, Depressive Disorder, Major/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Schizophrenia/genetics, Young Adult, Clinical psychology, MESH: Depressive Disorder, Major, TWIN, BF, Impulsivity, Psykiatri, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Journal Article, ddc:610, Bipolar disorder, Biological Psychiatry, METAANALYSIS, MESH: Borderline Personality Disorder, MESH: Adolescent, Depressive Disorder, Major, MESH: Humans, MESH: Adult, medicine.disease, Comorbidity, MESH: Male, MESH: Schizophrenia, 030227 psychiatry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, PATTERNS, RC0321, DPYD, MESH: Multifactorial Inheritance, COMORBIDITY, MESH: Female, 030217 neurology & neurosurgery
Abstract: Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
Published: 2017

218. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

Author: Emmi Tikkanen, Pascal Guénel, Rico Rueedi, Hamdi Mbarek, Gerardo Heiss, Hilary K. Finucane, Jing Hua Zhao, Peter K. Joshi, Mark I. McCarthy, Frank B. Hu, Stephen J. Chanock, Manjeet K. Bolla, Sandosh Padmanabhan, Vilmundur Gudnason, Chunyan He, Aarno Palotie, Reedik Mägi, Joe Dennis, Nicholas G. Martin, Behrooz Z. Alizadeh, Elisabeth Widen, Caroline Hayward, Penelope A. Lind, Magdalena Zoledziewska, Ayellet V. Segrè, Fergus J. Couch, Massimo Mangino, Melissa C. Southey, Immaculata De Vivo, Yongmei Liu, Ute Hamann, Angela Cox, Maartje J. Hooning, Iffat Rahman, Mitul Shah, Eric Boerwinkle, Matthias W. Beckmann, Catharina A. Hartman, Tanguy Corre, Kathryn L. Lunetta, Thérèse Truong, Anna Marie Mulligan, Caterina Barbieri, Robert Winqvist, Lili Milani, Cristina Menni, Frits R. Rosendaal, Pau Navarro, Christian Gieger, Ken K. Ong, Stig E. Bojesen, Susan M. Ring, Marjanka K. Schmidt, George McMahon, Deborah J. Thompson, Robert Karlsson, Nicholas J. Timpson, M. Arfan Ikram, Alexander Teumer, Jingmei Li, Christa Meisinger, Diana L. Cousminer, Doris Stöckl, Heli Nevanlinna, Teresa Nutile, Tim D. Spector, Eva Albrecht, Murielle Bochud, Linda Broer, Felix R. Day, Sven Bergmann, Renée de Mutsert, Nicholas J. Wareham, Marjo-Riitta Järvelin, Marzyeh Amini, Elisabeth Altmaier, Isabel dos-Santos-Silva, Peter Vollenweider, Douglas F. Easton, Tamara B. Harris, Ellen A. Nohr, Paul D.P. Pharoah, David J. Porteous, Jenny A. Visser, Ilja M. Nolte, Genevieve Lachance, Thomas Meitinger, Archie Campbell, Thomas Brüning, Graham G. Giles, Johan G. Eriksson, Nancy L. Pedersen, George Davey Smith, Gonneke Willemsen, Joanne M. Murabito, Francesco Cucca, Daniel I. Chasman, Eleonora Porcu, Nora Franceschini, Thibaud Boutin, Ulla Sovio, Roger L. Milne, Annette Peters, Lisette Stolk, Paul M. Ridker, Claudia Langenberg, Patrick Sulem, Toshiko Tanaka, Marike Gabrielson, Judith S. Brand, Unnur Thorsteindottir, Alison M. Dunning, Marina Ciullo, Julie E. Buring, Harold Snieder, Lude Franke, Meir J. Stampfer, Po-Ru Loh, Julian Peto, Ellen W. Demerath, Sheila Ulivi, Ivana Kolcic, Maristella Steri, Jouke J. Hottenga, Amanda B. Spurdle, Tõnu Esko, Katherine S. Pollard, Eulalia Catamo, Anneli Pouta, Kyriaki Michailidou, Dieter Flesch-Janys, James F. Wilson, Kamila Czene, Sean Whalen, Diether Lambrechts, Abhishek Sarkar, Laura Crisponi, Jonathan Tyrer, Antonietta Robino, Sara Lindström, Harald Grallert, Stefania Lenarduzzi, Peter Kraft, Patrik K. E. Magnusson, Lavinia Paternoster, Digna R. Velez Edwards, Mike A. Nalls, Per Hall, Joyce Y. Tung, Cinzia Sala, Lindsay Fernández-Rhodes, Ayush Giri, Hiltrud Brauch, André G. Uitterlinden, Alkes L. Price, Tracy A. O'Mara, Lynda M. Rose, John L. Hopper, David A. Hinds, Katherine S. Ruth, Arto Mannermaa, Uwe Völker, Rossella Sorice, Zoltán Kutalik, Debbie A Lawlor, Georgia Chenevix-Trench, Anna Murray, Albertine J. Oldehinkel, Bruce H. R. Wolffenbuttel, Hae Kyung Im, Dale R. Nyholt, Lenore J. Launer, Andres Metspalu, Irene L. Andrulis, Konstantin Strauch, Albert V. Smith, Daniela Toniolo, Eco J. C. de Geus, Jenny Chang-Claude, Marek Zygmunt, Dorret I. Boomsma, Harry Campbell, Peter Devilee, Henry Völzke, Daniela Ruggiero, Dennis O. Mook-Kanamori, John R. B. Perry, Javier Benitez, Grant W. Montgomery, David J. Hunter, David Karasik, Luigi Ferrucci, Emily Hallberg, Stefania Bandinelli, Hermann Brenner, Raymond Noordam, Sarah E. Medland, Peter A. Fasching, Qin Wang, Ilaria Gandin, Manolis Kellis, Hannes Helgason, Igor Rudan, Paolo Radice, Michela Traglia, Jian'an Luan, Robert A. Scott, Brumat Marco, Veronique Vitart, Kari Stefansson, Katharina E. Schraut, Ko Willems van Dijk, Ozren Polasek, Daniel F. Gudbjartsson, Natalia Perjakova, Joop S.E. Laven, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, Art and Culture, History, Antiquity, Day, Felix R., Thompson, Deborah J., Helgason, Hanne, Chasman, Daniel I., Finucane, Hilary, Sulem, Patrick, Ruth, Katherine S., Whalen, Sean, Sarkar, Abhishek K., Albrecht, Eva, Altmaier, Elisabeth, Amini, Marzyeh, Barbieri, CATERINA MARIA, Boutin, Thibaud, Campbell, Archie, Demerath, Ellen, Giri, Ayush, He, Chunyan, Hottenga, Jouke J., Karlsson, Robert, Kolcic, Ivana, Loh, Po Ru, Lunetta, Kathryn L., Mangino, Massimo, Brumat, Marco, Mcmahon, George, Medland, Sarah E., Nolte, Ilja M., Noordam, Raymond, Nutile, Teresa, Paternoster, Lavinia, Perjakova, Natalia, Porcu, Eleonora, Rose, Lynda M., Schraut, Katharina E., Segrã¨, Ayellet V., Smith, Albert V., Stolk, Lisette, Teumer, Alexander, Andrulis, Irene L., Bandinelli, Stefania, Beckmann, Matthias W., Benitez, Javier, Bergmann, Sven, Bochud, Murielle, Boerwinkle, Eric, Bojesen, Stig E., Bolla, Manjeet K., Brand, Judith S., Brauch, Hiltrud, Brenner, Hermann, Broer, Linda, Brã¼ning, Thoma, Buring, Julie E., Campbell, Harry, Catamo, Eulalia, Chanock, Stephen, Chenevix Trench, Georgia, Corre, Tanguy, Couch, Fergus J., Cousminer, Diana L., Cox, Angela, Crisponi, Laura, Czene, Kamila, Davey Smith, George, De Geus, Eco J. C. N., De Mutsert, Renã©e, De Vivo, Immaculata, Dennis, Joe, Devilee, Peter, Dos Santos Silva, Isabel, Dunning, Alison M., Eriksson, Johan G., Fasching, Peter A., FernÃ¡ndez Rhodes, Lindsay, Ferrucci, Luigi, Flesch Janys, Dieter, Franke, Lude, Gabrielson, Marike, Gandin, Ilaria, Giles, Graham G., Grallert, Harald, Gudbjartsson, Daniel F., Guã©nel, Pascal, Hall, Per, Hallberg, Emily, Hamann, Ute, Harris, Tamara B., Hartman, Catharina A., Heiss, Gerardo, Hooning, Maartje J., Hopper, John L., Hu, Frank, Hunter, David J., Ikram, M. Arfan, Im, Hae Kyung, Jã¤rvelin, Marjo Riitta, Joshi, Peter K., Karasik, David, Kellis, Manoli, Kutalik, Zoltan, Lachance, Genevieve, Lambrechts, Diether, Langenberg, Claudia, Launer, Lenore J., Laven, Joop S. E., Lenarduzzi, Stefania, Li, Jingmei, Lind, Penelope A., Lindstrom, Sara, Liu, Yongmei, Luan, Jian'An, Mã¤gi, Reedik, Mannermaa, Arto, Mbarek, Hamdi, Mccarthy, Mark I., Meisinger, Christa, Meitinger, Thoma, Menni, Cristina, Metspalu, Andre, Michailidou, Kyriaki, Milani, Lili, Milne, Roger L., Montgomery, Grant W., Mulligan, Anna M., Nalls, Mike A., Navarro, Pau, Nevanlinna, Heli, Nyholt, Dale R., Oldehinkel, Albertine J., O'Mara, Tracy A., Padmanabhan, Sandosh, Palotie, Aarno, Pedersen, Nancy, Peters, Annette, Peto, Julian, Pharoah, Paul D. P., Pouta, Anneli, Radice, Paolo, Rahman, Iffat, Ring, Susan M., Robino, Antonietta, Rosendaal, Frits R., Rudan, Igor, Rueedi, Rico, Ruggiero, Daniela, Sala, Cinzia F., Schmidt, Marjanka K., Scott, Robert A., Shah, Mitul, Sorice, Rossella, Southey, Melissa C., Sovio, Ulla, Stampfer, Meir, Steri, Maristella, Strauch, Konstantin, Tanaka, Toshiko, Tikkanen, Emmi, Timpson, Nicholas J., Traglia, Michela, Truong, Thã©rã¨se, Tyrer, Jonathan P., Uitterlinden, AndrÃ© G., Edwards, Digna R. Velez, Vitart, Veronique, Vã¶lker, Uwe, Vollenweider, Peter, Wang, Qin, Widen, Elisabeth, Van Dijk, Ko Willem, Willemsen, Gonneke, Winqvist, Robert, Wolffenbuttel, Bruce H. R., Zhao, Jing Hua, Zoledziewska, Magdalena, Zygmunt, Marek, Alizadeh, Behrooz Z., Boomsma, Dorret I., Ciullo, Marina, Cucca, Francesco, Esko, Tãµnu, Franceschini, Nora, Gieger, Christian, Gudnason, Vilmundur, Hayward, Caroline, Kraft, Peter, Lawlor, Debbie A., Magnusson, Patrik K. E., Martin, Nicholas G., Mook Kanamori, Dennis O., Nohr, Ellen A., Polasek, Ozren, Porteous, David, Price, Alkes L., Ridker, Paul M., Snieder, Harold, Spector, Tim D., Stã¶ckl, Dori, Toniolo, Daniela, Ulivi, Sheila, Visser, Jenny A., Vã¶lzke, Henry, Wareham, Nicholas J., Wilson, James F., LifeLines Cohort, Study, Interact, Consortium, Kconfab/aocs, Investigator, Endometrial Cancer Association, Consortium, Ovarian Cancer Association, Consortium, Practical, Consortium, Spurdle, Amanda B., Thorsteindottir, Unnur, Pollard, Katherine S., Easton, Douglas F., Tung, Joyce Y., Chang Claude, Jenny, Hinds, David, Murray, Anna, Murabito, Joanne M., Stefansson, Kari, Ong, Ken K., Perry, John R. B., Internal Medicine, Erasmus MC other, Medical Oncology, Epidemiology, Obstetrics & Gynecology, Day, Felix [0000-0003-3789-7651], Thompson, Deborah [0000-0003-1465-5799], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Pharoah, Paul [0000-0001-8494-732X], Sovio, Ulla [0000-0002-0799-1105], Tyrer, Jonathan [0000-0003-3724-4757], Zhao, Jing Hua [0000-0003-4930-3582], Wareham, Nicholas [0000-0003-1422-2993], Easton, Douglas [0000-0003-2444-3247], Ong, Kenneth [0000-0003-4689-7530], Perry, John [0000-0001-6483-3771], Apollo - University of Cambridge Repository, Massachusetts Institute of Technology. Department of Mathematics, and Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), Ovarian Cancer Association Consortium, LOCI, Genome-wide association study, cancer risk, Menarche/genetics, Bioinformatics, GWAS, menarche, puberty, Body Mass Index, Risk Factors, Neoplasms, Databases, Genetic, WIDE ASSOCIATION, Endometrial Cancer Association Consortium, Ribonucleoproteins/genetics, 2. Zero hunger, Genetics, Age Factors, Genetics GWAS menarche, reproductive disorders, Neoplasms/genetics, 3. Good health, Ribonucleoproteins, Menarche, MENDELIAN RANDOMIZATION, Intercellular Signaling Peptides and Proteins, GROWTH, Female, TRAITS, Population variance, Intercellular Signaling Peptides and Proteins/genetics, Adolescent, Ubiquitin-Protein Ligases, kConFab/AOCS Investigators, Quantitative Trait Loci, Quantitative trait locus, Biology, METABOLISM, INHERITANCE, Polymorphism, Single Nucleotide, PRACTICAL consortium, 03 medical and health sciences, Genomic Imprinting, SDG 3 - Good Health and Well-being, Mendelian randomization, REGRESSION, medicine, Journal Article, Humans, cancer, Genetic Predisposition to Disease, 1000 Genomes Project, Membrane Proteins/genetics, METAANALYSIS, Puberty, Calcium-Binding Proteins, Membrane Proteins, Cancer, InterAct Consortium, Heritability, medicine.disease, BODY-MASS INDEX, 030104 developmental biology, genome-wide association studies, Puberty/genetics, LifeLines Cohort Study, Genome-Wide Association Study
Abstract: The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P
Published: 2017

219. Ambulatory measurement of the ECG T-wave amplitude

Author: Melanie Neijts, Gonneke Willemsen, René van Lien, and Eco J. C. de Geus
Subjects: medicine.medical_specialty, Endocrine and Autonomic Systems, Cognitive Neuroscience, General Neuroscience, education, Experimental and Cognitive Psychology, Sitting, T wave amplitude, Neuropsychology and Physiological Psychology, Developmental Neuroscience, Neurology, Nighttime sleep, Internal medicine, Mental stress, Heart rate, Ambulatory, cardiovascular system, medicine, Cardiology, sense organs, skin and connective tissue diseases, Psychology, Biological Psychiatry
Abstract: Ambulatory recording of the preejection period (PEP) can be used to measure changes in cardiac sympathetic nervous system (SNS) activity under naturalistic conditions. Here, we test the ECG T-wave amplitude (TWA) as an alternative measure, using 24-h ambulatory monitoring of PEP and TWA in a sample of 564 healthy adults. The TWA showed a decrease in response to mental stress and a monotonic decrease from nighttime sleep to daytime sitting and more physically active behaviors. Within-participant changes in TWA were correlated with changes in the PEP across the standardized stressors (r = .42) and the unstandardized naturalistic conditions (mean r = .35). Partialling out changes in heart rate and vagal effects attenuated these correlations, but they remained significant. Ambulatory TWA cannot replace PEP, but simultaneous recording of TWA and PEP provides a more comprehensive picture of changes in cardiac SNS activity in real-life settings.
Published: 2014

220. Polygenic scores associated with educational attainment in adults predict educational achievement and ADHD symptoms in children

Author: Sang Hong Lee, Danielle Posthuma, Debbie A Lawlor, Michael B. Miller, Igor Rudan, Jürgen Wellmann, François Bastardot, Lawrence F. Bielak, Anu Realo, William G. Iacono, Lude Franke, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Jorma Viikari, Jennifer A. Smith, David R. Van Wagoner, Elizabeth G. Holliday, Veronique Vitart, Robert F. Krueger, Pamela A. F. Madden, Jan Emmanuel De, Andrew Heath, David Cesarini, Najaf Amin, Dale R. Nyholt, Juliette Harris, Nicholas J. Timpson, George Dedoussis, Stefania Bandinelli, W. Hoffmann, Albert V. Smith, Beate St Pourcain, Stavroula Kanoni, Martin F. Elderson, Maria Dimitriou, Jouke-Jan Hottenga, Min A. Jhun, Daniel S. Evans, Marjo-Riitta Järvelin, Lei Yu, Krista Fischer, Jae Hoon Sul, Jennifer R. Harris, Brenda W.J.H. Penninx, Antti-Pekka Sarin, Ida Surakka, Arpana Agrawal, Bo Jacobsson, Klaus Berger, Matt McGue, Christopher F. Chabris, Marisa Loitfelder, Veikko Salomaa, David Schlessinger, Mina K. Chung, Erik A. Ehli, Kati Kristiansson, Eva Albrecht, Niina Eklund, Aarno Palotie, Sarah E. Medland, Reinhold E. Schmidt, Kurt Lohman, Luigi Ferrucci, Osorio Meirelles, Ivana Kolcic, Vilmundur Gudnason, Nicholas G. Martin, Tomi E. Mäkinen, Robert M. Kirkpatrick, Thomas Illig, Peter M. Visscher, Håkon K. Gjessing, Sebastian E. Baumeister, Carla A. Ibrahim-Verbaas, Per Hall, Elisabeth Widen, Panos Deloukas, Ronny Myhre, Michelle N. Meyer, Jonathan P. Beauchamp, Caroline Hayward, Eveline L. de Zeeuw, Penelope A. Lind, Erik Ingelsson, Ian J. Deary, George Davey-Smith, Dalton Conley, Peter Lichtner, Cornelia M. van Duijn, Samuli Ripatti, Dena G. Hernandez, Albert Hofman, George McMahon, Thais S. Rizzi, Wei Zhao, Patrick K.E. Magnusson, Jingmei Li, Mariza de Andrade, Ben A. Oostra, Abdel Abdellaoui, Andres Metspalu, Patricia A. Peyser, Jessica D. Faul, David C. Liewald, Christina Holzapfel, Lydia Quaye, John Barnard, Meike Bartels, Christian Gieger, John P. Rice, Christiaan de Leeuw, Patricia A. Boyle, Nicholas D. Hastie, David R. Weir, Adriaan Hofman, Astanand Jugessur, Tamara B. Harris, Catharina E. M. van Beijsterveldt, Gail Davies, H.-Erich Wichmann, Lynn Cherkas, Polasek Ozren Polasek, Harm-Jan Westra, Yongmei Liu, Jari Lahti, Matthijs J. H. M. van der Loos, Rodney J. Scott, Gérard Waeber, Peter Vollenweider, Behrooz Z. Alizadeh, Frank J. A. van Rooij, Susan M. Ring, Judith M. Vonk, Lyle J. Palmer, Alexander Teumer, John M. Starr, Antonio Terracciano, Sara Hägg, Erkki Vartiainen, David Laibson, Eco J. C. de Geus, Mika Kähönen, Marco Masala, Peng Lin, Nicolas W. Martin, André G. Uitterlinden, Dorret I. Boomsma, Harry Campbell, Sutapa Mukherjee, Konstantin Shakhbazov, Henning Tiemeier, Zó Ltan Kutalik, Grant W. Montgomery, Eva Reinmaa, Aldo Rustichini, Wouter J. Peyrot, David M. Evans, Martin Preisig, Cornelius A. Rietveld, T.J. Glasner, J Kaprio, John Attia, Pedro Marques Vidal, Sharon L.R. Kardia, Peter K. Joshi, Toshiko Tanaka, Rauli Svento, Magnus Johannesson, Terho Lethimäki, Jüri Allik, Philip L. De Jager, Antti Latvala, Marja-Liisa Nuotio, Juha Karjalainen, Henry Völzke, Roy Thurik, Rolf Holle, Kelly S. Benke, Christopher Oldmeadow, Esko Toñu Esko, Johan G. Eriksson, Alan F. Wright, Francesco Cucca, Ute Bültmann, Olli T. Raitakari, Melissa E. Garcia, Patrick J. F. Groenen, Maria M. Groen-Blokhuis, Gonneke Willemsen, Jian Yang, Lili Milani, Fernando Rivadeneira, David A. Bennett, Gudny Eiriksdottir, Katri Räikkönen, Harold Snieder, Laura J. Bierut, James J. Hudziak, James F. Wilson, Rudolf S N Fehrmann, Jaime Derringer, Gareth E. Davies, K. Petrovic, Markus Perola, Lenore J. Launer, Daniel J. Benjamin, Paul Lichtenstein, Philipp Koellinger, Andreas Mielck, Jeffrey A. Boatman, Henrik Grönberg, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Public Health Research (PHR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), EMGO+ - Mental Health, Biological Psychology, Methods and Techniques, Child and Adolescent Psychiatry / Psychology, Ophthalmology, and Epidemiology
Subjects: Netherlands Twin Register (NTR), Multifactorial Inheritance, genetic association, genotype, Academic achievement, Educational achievement, single nucleotide polymorphism, genetic variability, Genetics (clinical), Netherlands, child, article, symptom, academic achievement, Psychiatry and Mental health, priority journal, achievement test, Regression Analysis, Psychology, SDG 4 - Quality Education, Clinical psychology, Adult, phenotype, effect size, attention deficit disorder, gene frequency, educational status, Cellular and Molecular Neuroscience, reading, study skills, mental disorders, Genetics, medicine, Humans, ADHD, Attention deficit hyperactivity disorder, Achievement test, controlled study, human, Association (psychology), Genetic association, attention disturbance, language, School performance, medicine.disease, arithmetic, major clinical study, Polygenic scores, Educational attainment, gene linkage disequilibrium, Attention Deficit Disorder with Hyperactivity, Study skills
Abstract: The American Psychiatric Association estimates that 3 to 7 per cent of all school aged children are diagnosed with attention deficit hyperactivity disorder (ADHD). Even after correcting for general cognitive ability, numerous studies report a negative association between ADHD and educational achievement. With polygenic scores we examined whether genetic variants that have a positive influence on educational attainment have a protective effect against ADHD. The effect sizes from a large GWA meta-analysis of educational attainment in adults were used to calculate polygenic scores in an independent sample of 12-year-old children from the Netherlands Twin Register. Linear mixed models showed that the polygenic scores significantly predicted educational achievement, school performance, ADHD symptoms and attention problems in children. These results confirm the genetic overlap between ADHD and educational achievement, indicating that one way to gain insight into genetic variants responsible for variation in ADHD is to include data on educational achievement, which are available at a larger scale. (C) 2014 Wiley Periodicals, Inc.
Published: 2014

221. Heritability of cardiac vagal control in 24-h heart rate variability recordings: Influence of ceiling effects at low heart rates

Author: Melanie Neijts, René van Lien, Nina Kupper, Gonneke Willemsen, Eco J. C. de Geus, and Dorret I. Boomsma
Subjects: medicine.medical_specialty, Endocrine and Autonomic Systems, Cognitive Neuroscience, General Neuroscience, Experimental and Cognitive Psychology, Heritability, Standard deviation, Neuropsychology and Physiological Psychology, Developmental Neuroscience, Neurology, Internal medicine, Ambulatory, medicine, Cardiology, Heart rate variability, Ceiling effect, Vagal tone, Psychology, Biological Psychiatry, circulatory and respiratory physiology, Interbeat interval
Abstract: This study estimated the heritability of 24-h heart rate variability (HRV) measures, while considering ceiling effects on HRV at low heart rates during the night. HRV was indexed by the standard deviation of all valid interbeat intervals (SDNN), the root mean square of differences between valid, successive interbeat intervals (RMSSD), and peak-valley respiratory sinus arrhythmia (pvRSA). Sleep and waking levels of cardiac vagal control were assessed in 1,003 twins and 285 of their non-twin siblings. Comparable heritability estimates were found for SDNN (46%‐53%), RMSSD (49%‐ 54%), and pvRSA (48%‐57%) during the day and night.Anighttime ceiling effect was revealed in 10.7% of participants by a quadratic relationship between mean pvRSA and the interbeat interval. Excluding these participants did not change the heritability estimates.The genetic factors influencing ambulatory pvRSA, RMSSD, and SDNN largely overlap.These results suggest that gene-finding studies may pool the different cardiac vagal indices and that exclusion of participants with low heart rates is not required. Descriptors: Parasympathetic nervous system, Ambulatory monitoring, RSA, RMSSD, Twins
Published: 2014

222. Polygenic risk scores for smoking: predictors for alcohol and cannabis use?

Author: Jacqueline M. Vink, Helena Furberg, Gonneke Willemsen, Michael C. Neale, Dorret I. Boomsma, Jouke-Jan Hottenga, and Eco J. C. de Geus
Subjects: medicine.medical_specialty, biology, business.industry, medicine.medical_treatment, Medicine (miscellaneous), Regression analysis, Heritability, biology.organism_classification, medicine.disease, Comorbidity, 3. Good health, Psychiatry and Mental health, medicine, Smoking cessation, Cannabis, Allele, Age of onset, Young adult, business, Psychiatry
Abstract: Background and Aims A strong correlation exists between smoking and the use of alcohol and cannabis.This paper uses polygenic risk scores to explore the possibility of overlapping genetic factors.Those scores reflect a combined effect of selected risk alleles for smoking. Methods Summary-level P-values were available for smoking initiation, age at onset of smoking, cigarettes per day and smoking cessation from the Tobacco and Genetics Consortium (n between 22 000and70 000subjects).UsingdifferentP-valuethresholds(0.1,0.2and0.5)fromthemeta-analysis,setsof 'risk alleles' were defined and used to generate a polygenic risk score (weighted sum of the alleles) for each subject in an independent target sample from the Netherlands Twin Register (n = 1583). The association between polygenic smoking scores and alcohol/cannabis use was investigated with regression analysis. Results The polygenic scores for 'cigarettes per day' were associated significantly with the number of glasses alcohol per week (P = 0.005, R 2 = 0.4- 0.5%) and cannabis initiation (P = 0.004, R 2 = 0.6-0.9%). The polygenic scores for 'age at onset of smoking' were associated significantly with 'age at regular drinking' (P = 0.001, R 2 = 1.1-1.5%), while the scores for 'smoking initiation' and 'smoking cessation' did not significantly predict alcohol or cannabis use. Conclusions Smoking, alcohol and cannabis use are influenced by aggregated genetic risk factors shared between these substances.The many common genetic variants each have a very small individual effect size.
Published: 2014

223. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels: Evidence for correlated genetic effects

Author: Gonneke Willemsen, Michel R.T. Sinke, Jacoline Neuteboom, Marleen H. M. de Moor, Gitta H. Lubke, Jenny H. D. A. van Beek, Dorret I. Boomsma, Jacqueline M. Vink, Eco J. C. de Geus, Cornelis Kluft, Lot M. Geels, Biological Psychology, Clinical Child and Family Studies, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Adult, Male, Netherlands Twin Register (NTR), Alcohol Drinking, Population level, Twins, Physiology, Alcohol, Toxicology, digestive system, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Gamma glutamyl transferase, SDG 3 - Good Health and Well-being, Genetic Pleiotropy, Humans, Pharmacology (medical), Longitudinal Studies, Registries, Gamma-glutamyltransferase, Aged, Netherlands, 030304 developmental biology, Aged, 80 and over, Pharmacology, 0303 health sciences, biology, Data Collection, Causal effect, gamma-Glutamyltransferase, Middle Aged, Heritability, digestive system diseases, 3. Good health, Psychiatry and Mental health, chemistry, biology.protein, Female, Alcohol intake, Biomarkers, 030217 neurology & neurosurgery
Abstract: Background: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT to alcohol use, which may result from genetic differences between individuals. This study aimed to determine whether the epidemiological association between alcohol intake and GGT at the population level is necessarily a causal one or may also reflect effects of genetic pleiotropy (genes influencing multiple traits). Methods: Data on alcohol intake (grams alcohol/day) and GGT, originating from twins, their siblings and parents (N= 6465) were analyzed with structural equation models. Bivariate genetic models tested whether genetic and environmental factors influencing alcohol intake and GGT correlated significantly. Significant genetic and environmental correlations are consistent with a causal model. If only the genetic correlation is significant, this is evidence for genetic pleiotropy. Results: Phenotypic correlations between alcohol intake and GGT were significant in men (r= .17) and women (r= .09). The genetic factors underlying alcohol intake correlated significantly with those for GGT, whereas the environmental factors were weakly correlated (explaining 4-7% vs. 1-2% of the variance in GGT respectively). Conclusions: In this healthy population sample, the epidemiological association of alcohol intake with GGT is at least partly explained by genetic pleiotropy. Future longitudinal twin studies should determine whether a causal mechanism underlying this association might be confined to heavy drinking populations. © 2013 Elsevier Ireland Ltd.
Published: 2014

224. Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Author: Michele L. Pergadia, Grant W. Montgomery, Nicholas G. Martin, Lannie Ligthart, Cathryn M. Lewis, Ian W. Craig, Gerome Breen, Jouke-Jan Hottenga, Dorret I. Boomsma, Gonneke Willemsen, Enda M. Byrne, Pamela A. F. Madden, Anne Farmer, Peter McGuffin, Christel M. Middeldorp, Brenda W.J.H. Penninx, Jacqueline M. Vink, Dale R. Nyholt, Andrew C. Heath, EMGO+ - Mental Health, Biological Psychology, Psychiatry, and EMGO - Mental health
Subjects: Adult, Male, Netherlands Twin Register (NTR), medicine.medical_specialty, Multifactorial Inheritance, Migraine Disorders, Genome-wide association study, Comorbidity, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, Interviews as Topic, Young Adult, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, mental disorders, Genetics, medicine, Humans, Genetic Testing, Genetics (clinical), Depression (differential diagnoses), Genetic association, Genetic testing, Netherlands, Depressive Disorder, Major, medicine.diagnostic_test, Australia, Middle Aged, medicine.disease, Twin study, 3. Good health, Migraine, Major depressive disorder, Female, Genome-Wide Association Study
Abstract: Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. © 2013 Springer-Verlag Berlin Heidelberg.
Published: 2014

225. The Dopaminergic Reward System and Leisure Time Exercise Behavior: A Candidate Allele Study

Author: James J. Hudziak, Catharina E. M. van Beijsterveldt, Eco J. C. de Geus, Charlotte Huppertz, Gareth E. Davies, Conor V. Dolan, Meike Bartels, Maria M. Groen-Blokhuis, Gonneke Willemsen, Xiangjun Xiao, Marleen H. M. de Moor, Jouke-Jan Hottenga, Erik A. Ehli, A. Abdellaoui, Paul Scheet, Dorret I. Boomsma, Biological Psychology, Clinical Child and Family Studies, EMGO+ - Lifestyle, Overweight and Diabetes, Epidemiology, and Child and Adolescent Psychiatry / Psychology
Subjects: Adult, Male, Netherlands Twin Register (NTR), Adolescent, Genotype, Article Subject, Dopamine, Health Behavior, lcsh:Medicine, Single-nucleotide polymorphism, Minisatellite Repeats, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Receptors, Dopamine, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Reward, Genetic variation, Humans, Computer Simulation, Registries, Allele, Child, Exercise, Life Style, Alleles, Netherlands, 030304 developmental biology, Genetic association, Genetics, 0303 health sciences, General Immunology and Microbiology, lcsh:R, Genetic Variation, General Medicine, Middle Aged, Heritability, Twin study, Variable number tandem repeat, Phenotype, Female, Algorithms, 030217 neurology & neurosurgery, Research Article, rs4680
Abstract: Purpose. Twin studies provide evidence that genetic influences contribute strongly to individual differences in exercise behavior. We hypothesize that part of this heritability is explained by genetic variation in the dopaminergic reward system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2: rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and in COMT: rs4680) and three variable number of tandem repeats (VNTRs inDRD4, upstream ofDRD5, and inDAT1) were investigated for an association with regular leisure time exercise behavior.Materials and Methods. Data on exercise activities and at least one SNP/VNTR were available for 8,768 individuals aged 7 to 50 years old that were part of the Netherlands Twin Register. Exercise behavior was quantified as weekly metabolic equivalents of task (MET) spent on exercise activities. Mixed models were fitted in SPSS with genetic relatedness as a random effect.Results. None of the genetic variants were associated with exercise behavior (P>.02), despite sufficient power to detect small effects.Discussion and Conclusions. We did not confirm that allelic variants involved in dopaminergic function play a role in creating individual differences in exercise behavior. A plea is made for large genome-wide association studies to unravel the genetic pathways that affect this health-enhancing behavior.
Published: 2014

226. Telomere Length in Circulating Leukocytes is Associated with Lung Function and Disease

Author: Alexessander Couto Alves, Kirsi H. Pietiläinen, Cornelia M. van Duijn, Pamela A. F. Madden, Massimo Mangino, Iiris Hovatta, Stefan Karrasch, Alexandra I. F. Blakemore, Anjali K. Henders, Marjo-Riitta Järvelin, Ben A. Oostra, Seppo Sarna, Annette Peters, Eco J. C. de Geus, H.-Erich Wichmann, Ana Viñuela, Nilesh J. Samani, Christopher P. Nelson, Linda Broer, Elina Sillanpää, Ida Surakka, Christian Gieger, Konstantin Strauch, Jessica L. Buxton, Markku Peltonen, Taina Rantanen, Sarianna Sipilä, Holger Schulz, Eva Albrecht, Nicholas G. Martin, Veryan Codd, Patrik K. E. Magnusson, Jaakko Kaprio, Melanie Waldenberger, Nancy L. Pedersen, Najaf Amin, Gonneke Willemsen, Dale R. Nyholt, Rudolf A. Jörres, Joachim Heinrich, Dorret I. Boomsma, Juergen Behr, Manuel A. R. Ferreira, Hell M. Backmand, Päivi Piirilä, Tim D. Spector, Aila Rissanen, Tellervo Korhonen, Rudolf M. Huber, Sara Hägg, Epidemiology, Clinical Genetics, Public Health, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Lung Diseases, Male, Pulmonary and Respiratory Medicine, Spirometry, Netherlands Twin Register (NTR), Vital capacity, Vital Capacity, ennenaikainen vanheneminen, Disease, Cohort Studies, Pathogenesis, Pulmonary Disease, Chronic Obstructive, Telomere Homeostasis, SDG 3 - Good Health and Well-being, Forced Expiratory Volume, astma, Leukocytes, Humans, COPD, Medicine, keuhkoahtaumatauti, Aged, Asthma, telomeeri, medicine.diagnostic_test, premature aging, business.industry, Smoking, Case-control study, ta3141, Middle Aged, Telomere, spirometria, medicine.disease, biologinen ikä, biological age, 3. Good health, respiratory tract diseases, Europe, Case-Control Studies, Immunology, Regression Analysis, Female, business
Abstract: Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
Published: 2014

227. The Genome of the Netherlands: design, and project goals

Author: Elisabeth M. van Leeuwen, Jeroen F. J. Laros, Clara C. Elbers, Alexandros Kanterakis, Jessica van Setten, Cisca Wijmenga, Gonneke Willemsen, Vyacheslav Koval, Qibin Li, Sujie Cao, Jouke-Jan Hottenga, Jayne Y. Hehir-Kwa, Laurent C. Francioli, Kai Ye, Jeanine J. Houwing-Duistermaat, Morris A. Swertz, David van Enckevort, Sara L. Pulit, Karol Estrada, Hailiang Mai, Marian Beekman, Anton J. M. de Craen, Gert-Jan B. van Ommen, Ben A. Oostra, Androniki Menelaou, Hongzhi Cao, Martijn Dijkstra, Mathijs Kattenberg, Abdel Abdellaoui, Yingrui Li, Albert Hofman, Cornelia M. van Duijn, Martijn Vermaat, Eline Slagboom, Lennart C. Karssen, Johan T. den Dunnen, Freerk van Dijk, Fernanodo Rivadeneira, Dorret I. Boomsma, Ruoyan Chen, Patrick Deelen, Paul I.W. de Bakker, Peter de Knijff, Bruce H. R. Wolffenbuttel, Ning Li, Heorhiy Byelas, Victor Guryev, Yuanping Du, Pieter B. Neerincx, André G. Uitterlinden, Jun Wang, H. Eka D. Suchiman, Epidemiology, Dermatology, Molecular Genetics, Internal Medicine, Clinical Genetics, Biological Psychology, EMGO+ - Mental Health, Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Adult Psychiatry
Subjects: Adult, Male, Netherlands Twin Register (NTR), TWIN, Population genetics, Computational biology, Human genetic variation, Biology, whole-genome sequence, Genome, DISEASE, Article, COMMON SNPS, Young Adult, Gene Frequency, Databases, Genetic, Genetic variation, Genetics, WIDE ASSOCIATION, Humans, Genetics (clinical), SUSCEPTIBILITY VARIANTS, Aged, Netherlands, Genetic association, RISK, Aged, 80 and over, HERITABILITY, MUTATIONS, Genome, Human, Haplotype, Genetic Variation, High-Throughput Nucleotide Sequencing, population genetics, Sequence Analysis, DNA, Middle Aged, Biobank, FAMILY, Phylogeography, Female, Imputation (genetics), trio-design
Abstract: Within the Netherlands a national network of biobanks has been established (Biobanking and Biomolecular Research Infrastructure-Netherlands (BBMRI-NL)) as a national node of the European BBMRI. One of the aims of BBMRI-NL is to enrich biobanks with different types of molecular and phenotype data. Here, we describe the Genome of the Netherlands (GoNL), one of the projects within BBMRI-NL. GoNL is a whole-genome-sequencing project in a representative sample consisting of 250 trio-families from all provinces in the Netherlands, which aims to characterize DNA sequence variation in the Dutch population. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. The family-based design represents a unique resource to assess the frequency of regional variants, accurately reconstruct haplotypes by family-based phasing, characterize short indels and complex structural variants, and establish the rate of de novo mutational events. GoNL will also serve as a reference panel for imputation in the available genome-wide association studies in Dutch and other cohorts to refine association signals and uncover population-specific variants. GoNL will create a catalog of human genetic variation in this sample that is uniquely characterized with respect to micro-geographic location and a wide range of phenotypes. The resource will be made available to the research and medical community to guide the interpretation of sequencing projects. The present paper summarizes the global characteristics of the project. © 2014 Macmillan Publishers Limited All rights reserved.
Published: 2014

228. Multi-ethnic fine-mapping of 14 central adiposity loci

Author: Eco De Geus, Michael Weedon, Joyce Van Meurs, Torben Jørgensen, Kirsi Pietiläinen, Patricia Munroe, Amanda Bennett, Michael Stumvoll, Andrew Hattersley, Vilmundur Gudnason, Dale Nyholt, Mary Feitosa, Mariano Dei, Marcus Dörr, Terho Lehtimäki, Anette P Gjesing, Daniel Witte, Adebowale Adeyemo, Eleanor Wheeler, Peter Kovacs, Hana Lango Allen, Philippe Froguel, Panos Deloukas, Cornelia Van Duijn, Tiinamaija Tuomi, Daniel Shriner, Struan Grant, Tonu Esko, Reedik Mägi, Lyle John Palmer, L. Adrienne Cupples, Claes Ohlsson, Krina Zondervan, Thomas Meitinger, Sarah Nyante, Lina Zgaga, Themistocles Assimes, Paul Elliott, Robert Luben, Albert Vernon Smith, MANUELA UDA, Rona Strawbridge, Richard Bergman, Gonneke Willemsen, Igor Rudan, Maris Teder-Laving, Liesbeth Vandenput, Mary Cushman, Allan Linneberg, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Netherlands Twin Register (NTR), Linkage disequilibrium, Ethnic group, Churg-strauss syndrome, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, waist-to-hip ratio, multi-ethnic fine-mapping, Genetics, medicine, Ethnicity, Humans, Molecular Biology, Genetics (clinical), Adiposity, Anthropometry, Association Studies Articles, Physical Chromosome Mapping, Computational Biology, Molecular Sequence Annotation, General Medicine, medicine.disease, Carotid sinus syncope, Genetic Loci, Central Adiposity, Allelic heterogeneity
Abstract: The Genetic Investigation of Anthropometric Traits (GIANT) consortium identified 14 loci in European Ancestry (EA) individuals associated with waist-to-hip ratio (WHR) adjusted for body mass index. These loci are wide and narrowingthe signalsremains necessary. Twelve of 14 loci identified inGIANTEA samples retained strong associations with WHR in our joint EA/individuals of African Ancestry (AA) analysis (log-Bayes factor >6.1). Transethnic analysesatfiveloci (TBX15-WARS2, LYPLAL1, ADAMTS9, LY86andITPR2-SSPN)substantially narrowed the signals to smaller sets of variants, some of which are in regions that have evidence of regulatory activity. By leveraging varying linkage disequilibrium structures across different populations, single-nucleotide polymorphisms (SNPs) with strong signals and narrower credible sets from trans-ethnic meta-analysis of central obesity provide more precise localizations of potential functional variants and suggest a possible regulatory role. Meta-analysis results for WHR were obtained from 77 167 EA participants from GIANT and 23 564 AA participants from the AfricanAncestry Anthropometry Genetics Consortium. For fine mapping we interrogatedSNPs within ±250 kbflanking regionsof 14 previously reported indexSNPsfrom loci discovered in EApopulations by performing trans-ethnic meta-analysis of results from the EA and AA meta-analyses. We applied a Bayesian approach that leverages allelic heterogeneity across populations to combine meta-analysis results and aids in fine-mapping shared variants at these locations. We annotated variants using information from the ENCODE Consortium and Roadmap Epigenomics Project to prioritize variants for possible functionality. © The Author 2014. Published by Oxford University Press. All rights reserved.
Published: 2014

229. A twin-sibling study on the relationship between exercise attitudes and exercise behavior

Author: Meike Bartels, Gonneke Willemsen, Eco J. C. de Geus, Marleen H. M. de Moor, Iris E. Jansen, Dorret I. Boomsma, Charlotte Huppertz, Human genetics, EMGO - Lifestyle, overweight and diabetes, Radiology & Nuclear Medicine, Biological Psychology, Clinical Child and Family Studies, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Adult, Male, Netherlands Twin Register (NTR), Adolescent, media_common.quotation_subject, Health Behavior, Embarrassment, Bivariate analysis, Article, Developmental psychology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Genetics, Humans, Young adult, 10. No inequality, Association (psychology), Exercise, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, media_common, Principal Component Analysis, Siblings, 030229 sport sciences, Twins, Monozygotic, Heritability, Middle Aged, Twin study, Health psychology, Female, Psychology, 030217 neurology & neurosurgery, Social cognitive theory
Abstract: Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a significant influence of genetic factors on regular exercise behavior. This twin-sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18-50 years). A genetic contribution was found for exercise behavior (50 % in males, 43 % in females) and for the six exercise attitude components derived from principal component analysis: perceived benefits (21, 27 %), lack of skills, support and/or resources (45, 48 %), time constraints (25, 30 %), lack of energy (34, 44 %), lack of enjoyment (47, 44 %), and embarrassment (42, 49 %). These components were predictive of leisure time exercise behavior (R(2) = 28 %). Bivariate modeling further showed that all the genetic (0.36 < |rA| < 0.80) and all but two unique environmental (0.00 < |rE| < 0.27) correlations between exercise attitudes and exercise behavior were significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins' difference scores were in line with this finding. It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior.
Published: 2014

230. Explaining Individual Differences in Alcohol Intake in Adults: Evidence for Genetic and Cultural Transmission?

Author: Dorret I. Boomsma, Marleen H. M. de Moor, Gonneke Willemsen, Jenny H. D. A. van Beek, Lot M. Geels, Biological Psychology, Clinical Child and Family Studies, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Adult, Male, Netherlands Twin Register (NTR), Health (social science), Adolescent, Alcohol Drinking, Offspring, Population, Culture, Individuality, Toxicology, Affect (psychology), Structural equation modeling, Developmental psychology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Humans, Longitudinal Studies, Registries, education, Cultural transmission in animals, 030304 developmental biology, Aged, Netherlands, Aged, 80 and over, 0303 health sciences, education.field_of_study, Heritability, Middle Aged, Psychiatry and Mental health, Alcohol intake, Female, Psychology, 030217 neurology & neurosurgery, Demography
Abstract: The current study aimed to describe what proportion of variation in adult alcohol intake is attributable to genetic differences among individuals and what proportion to differences in environmental experiences individuals have been exposed to. Effects of age, gender, spousal resemblance, and cultural transmission of alcohol intake from parents to offspring were taken into account.In a twin-family design, the effects of genetic and cultural transmission and shared and nonshared environment on alcohol intake were estimated with genetic structural equation models. Data originated from adult twins, their siblings, parents (n = 12,587), and spouses (n = 429) registered with the population-based Netherlands Twin Register (63.5% female; ages 18-97 years).Alcohol intake (grams per day) was higher among men than women and increased with age. Broad-sense heritability estimates were similar across sex and age (53%). Spousal resemblance was observed (r = .39) but did not significantly affect the heritability estimates. No effects of cultural transmission were detected. In total, 23% of the variation in alcohol intake was explained by additive genetic effects, 30% by dominant (nonadditive) gene action, and 47% by environmental effects that were not shared among family members.Individual differences in adult alcohol intake are explained by genetic and individual-specific environmental effects. The same genes are expressed in males and females and in younger and older participants. A substantial part of the heritability of alcohol intake is attributable to nonadditive gene action. Effects of cultural transmission that have been reported in adolescence are not present in adulthood.
Published: 2014

231. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Author: Paul Lichtenstein, Tessa L. Cutler, Catherine Derom, William S. Kremen, Corrado Fagnani, Ruth J. F. Loos, Yoon-Mi Hur, Kirsten Ohm Kyvik, Lucía Colodro-Conde, Hoe Uk Jeong, Gombojav Bayasgalan, Kauko Heikkilä, Nicholas G. Martin, Aline Jelenkovic, Karri Silventoinen, Margaret Gatz, Zengchang Pang, Dongfeng Zhang, Judy L. Silberg, Fujio Inui, Grant W. Montgomery, Shandell Pahlen, David Laszlo Tarnoki, Thalia C. Eley, Cristina D'Ippolito, Sevgi Y. Öncel, Gonneke Willemsen, Sari Aaltonen, Amie E. Hwang, Juan F. Sánchez-Romera, Yun Mi Song, Andreas Busjahn, Esther Rebato, Finn Rasmussen, Chika Honda, Robert F. Krueger, David A. Butler, Patrik K. E. Magnusson, Axel Skytthe, Yoshie Yokoyama, Tim D. Spector, Qihua Tan, Catherine Tuvblad, Mikio Watanabe, Jacob v. B. Hjelmborg, Genevieve Lachance, Ruth Krasnow, Sarah E. Medland, Tom A. McAdams, Michael J. Lyons, Ingunn Brandt, Yoshinori Iwatani, Danshiitsoodol Narandalai, Robert F. Vlietinck, Laura A. Baker, Fazil Aliev, Carol E. Franz, Thorkild I. A. Sørensen, Alice M. Gregory, Jennifer R. Harris, Jaakko Kaprio, Matt McGue, Nancy L. Pedersen, Reijo Sund, Brooke M. Huibregtse, Maria A. Stazi, Kayoung Lee, Toos C. E. M. van Beijsterveldt, Hermine H. Maes, S. Alexandra Burt, Anna K. Dahl-Aslan, Kelly L. Klump, Tracy L. Nelson, Gary E. Swan, John L. Hopper, Thomas M. Mack, Kaare Christensen, Joohon Sung, Christian Kandler, Robin P. Corley, Dedra Buchwald, Kerry L. Jang, Juan R. Ordoñana, Massimo Mangino, Lindon J. Eaves, Sisira Siribaddana, Athula Sumathipala, Dorret I. Boomsma, Adam Domonkos Tarnoki, Thomas Sevenius Nilsen, Fruhling Rijsdijk, Keith E. Whitfield, Wendy Cozen, Glen E. Duncan, Matthew Hotopf, Sarah Yang, Meike Bartels, Jack H. Goldberg, Per Tynelius, Biological Psychology, EMGO+ - Musculoskeletal Health, Franco, Eduardo, Kırıkkale Üniversitesi, Department of Social Research (2010-2017), Department of Public Health, Clinicum, Jaakko Kaprio / Principal Investigator, Institute for Molecular Medicine Finland, Sociology, Population Research Unit (PRU), and Genetic Epidemiology
Subjects: Male, Netherlands Twin Register (NTR), 0301 basic medicine, medicine, LOCI, heritability, Standard of living, Global Health, Cohort Studies, Evolutionsbiologi, 0302 clinical medicine, genetic variability, Medicine and Health Sciences, Biology (General), Aged, 80 and over, birth cohorts, education.field_of_study, adult, General Neuroscience, WOMEN, human biology, twins, General Medicine, Environmental exposure, Middle Aged, Hälsovetenskaper, 3142 Public health care science, environmental and occupational health, Europe, female, 5141 Sociology, Female, Utvecklingsbiologi, TWIN COHORTS, TRAITS, Adult, Asia, QH301-705.5, Science, Population, Short Report, 030209 endocrinology & metabolism, Biology, General Biochemistry, Genetics and Molecular Biology, CODATwins project, Young Adult, 03 medical and health sciences, AGE, male, Behavioral Sciences Biology, Human biology, Health Sciences, Genetic variation, Genetics, Humans, human, GENOME-WIDE ASSOCIATION, Genetik, Human height, Human Biology and Medicine, education, Etologi, Aged, Evolutionary Biology, General Immunology and Microbiology, INFANT-MORTALITY, Australia, Biology and Life Sciences, Environmental Exposure, Heritability, Body Height, BODY-MASS INDEX, 030104 developmental biology, Earth and Environmental Sciences, North America, RA, Body mass index, height, meta analysis, Developmental Biology, Demography
Abstract: Heikkila, Kauko/0000-0002-9256-8028; McAdams, Tom/0000-0002-6825-3499; Ordonana, Juan R./0000-0001-7779-6017; Siribaddana, Sisira/0000-0001-5821-2557; Tan, Qihua/0000-0003-3194-0030; Skytthe, Axel E/0000-0002-8629-4913; Hjelmborg, Jacob/0000-0001-9630-9149; Kaprio, Jaakko/0000-0002-3716-2455; Loos, Ruth J F/0000-0002-8532-5087; ONCEL, Sevgi YURT/0000-0002-0990-292X; Fagnani, Corrado/0000-0001-5771-7772; mangino, massimo/0000-0002-2167-7470; Colodro-Conde, Lucia/0000-0002-9004-364X; Kandler, Christian/0000-0002-9175-235X; ROMERA, JUAN FRANCISCO SANCHEZ/0000-0002-5405-6216; Montgomery, Grant W/0000-0002-4140-8139; Medland, Sarah E/0000-0003-1382-380X; Christensen, Kaare/0000-0002-5429-5292; Aliev, Fazil/0000-0001-8357-4699; Huibregtse, Brooke M./0000-0003-0977-7249; Busjahn, Andreas/0000-0001-9650-6919; Tan, Qihua/0000-0003-3194-0030; Sund, Reijo/0000-0002-6268-8117; Kremen, William/0000-0002-8629-5609; Pahlen, Shandell/0000-0003-0753-4155; Rasmussen, Finn/0000-0001-7915-7809; Franz, Carol/0000-0002-8987-1755; Pedersen, Nancy/0000-0001-8057-3543; Aaltonen, Sari/0000-0002-2873-4263; Hotopf, Matthew/0000-0002-3980-4466; Rebato, Esther/0000-0003-1221-8501; Kyvik, Kirsten Ohm/0000-0003-2981-0245; Rijsdijk, Fruhling/0000-0003-4762-2803; Silventoinen, Karri/0000-0003-1759-3079 WOS: 000391277600001 PubMed: 27964777 Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 18861994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve. Suomen Akatemia [266592] Suomen Akatemia 266592 Karri Silventoinenr The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Published: 2016

232. Validated inference of smoking habits from blood with a finite DNA methylation marker set

Author: Dorret I. Boomsma, Silvana C.E. Maas, Janine F. Felix, Diana van Heemst, Sonja Kunze, Oscar H. Franco, Melanie Waldenberger, Fan Liu, Leonard H. van den Berg, P. Eline Slagboom, Joyce B. J. van Meurs, Alexander Teumer, Rory P. Wilson, Jenny van Dongen, Eco J. C. de Geus, Mohsen Ghanbari, Manfred Kayser, Annette Peters, Vincent W. V. Jaddoe, Liesbeth Duijts, Marian Beekman, Carla J.H. van der Kallen, M. Arfan Ikram, Gonneke Willemsen, Hans J. Grabe, Karl-Heinz Ladwig, Athina Vidaki, André G. Uitterlinden, Interne Geneeskunde, RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, RS: CARIM - R3 - Vascular biology, Epidemiology, Genetic Identification, Internal Medicine, Pediatrics, Erasmus MC other, Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, and APH - Personalized Medicine
Subjects: Epigenomics, Male, BIOMARKER, Netherlands Twin Register (NTR), Passive smoking, HYPOMETHYLATION, Epidemiology, medicine.medical_treatment, Inference, 030204 cardiovascular system & hematology, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, Methods, Medicine, 030212 general & internal medicine, MATERNAL SMOKING, education.field_of_study, DNA methylation, NEWBORNS, Smoking, Area under the curve, 3. Good health, COTININE, Area Under Curve, Cohort, Female, Epigenetics, Adult, medicine.medical_specialty, Population, Smoking inference, Sensitivity and Specificity, 03 medical and health sciences, SDG 3 - Good Health and Well-being, SELF-REPORTED SMOKING, Journal Article, Humans, EXPOSURE, TOBACCO-SMOKING, education, Forensics, EPIGENOME-WIDE ASSOCIATION, business.industry, Reproducibility of Results, DNA, chemistry, Smoking cessation, Smoking Cessation, CIGARETTE-SMOKING, business, Cotinine, Biomarkers, Demography
Abstract: Inferring a person’s smoking habit and history from blood is relevant for complementing or replacing self-reports in epidemiological and public health research, and for forensic applications. However, a finite DNA methylation marker set and a validated statistical model based on a large dataset are not yet available. Employing 14 epigenome-wide association studies for marker discovery, and using data from six population-based cohorts (N = 3764) for model building, we identified 13 CpGs most suitable for inferring smoking versus non-smoking status from blood with a cumulative Area Under the Curve (AUC) of 0.901. Internal fivefold cross-validation yielded an average AUC of 0.897 ± 0.137, while external model validation in an independent population-based cohort (N = 1608) achieved an AUC of 0.911. These 13 CpGs also provided accurate inference of current (average AUCcrossvalidation 0.925 ± 0.021, AUCexternalvalidation0.914), former (0.766 ± 0.023, 0.699) and never smoking (0.830 ± 0.019, 0.781) status, allowed inferring pack-years in current smokers (10 pack-years 0.800 ± 0.068, 0.796; 15 pack-years 0.767 ± 0.102, 0.752) and inferring smoking cessation time in former smokers (5 years 0.774 ± 0.024, 0.760; 10 years 0.766 ± 0.033, 0.764; 15 years 0.767 ± 0.020, 0.754). Model application to children revealed highly accurate inference of the true non-smoking status (6 years of age: accuracy 0.994, N = 355; 10 years: 0.994, N = 309), suggesting prenatal and passive smoking exposure having no impact on model applications in adults. The finite set of DNA methylation markers allow accurate inference of smoking habit, with comparable accuracy as plasma cotinine use, and smoking history from blood, which we envision becoming useful in epidemiology and public health research, and in medical and forensic applications. Electronic supplementary material The online version of this article (10.1007/s10654-019-00555-w) contains supplementary material, which is available to authorized users.
Published: 2019

233. Publisher Correction: Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Author: Gu Zhu, Cornelia M. van Duijn, M. Arfan Ikram, Alessia Visconti, Maria Pina Concas, Veronique Bataille, Nicholas G. Martin, George Davey Smith, Merel A. Hamer, Gonneke Willemsen, Massimiliano Cocca, Fan Liu, Marco Brumat, Antonietta Robino, Bochao D. Lin, Pirro G. Hysi, Tamar Nijsten, Changqing Zeng, Scott D. Gordon, Ilaria Gandin, David M. Evans, Dorret I. Boomsma, Susan M. Ring, Mario Falchi, Yan Chen, Alex W. Hewitt, Gibran Hemani, Jouke-Jan Hottenga, Seyhan Yazar, Tim D. Spector, David L. Duffy, Nicholas A. Furlotte, André G. Uitterlinden, Paolo Gasparini, Sarah E. Medland, Dragana Vuckovic, Giorgia Girotto, Cinzia Sala, David A. Mackey, George McMahon, Daniela Toniolo, Manfred Kayser, David A. Hinds, Ana M. Valdes, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Methodology
Subjects: Netherlands Twin Register (NTR), Variation (linguistics), Meta-analysis, Published Erratum, Genetics, Fraction (mathematics), Genome-wide association study, Biology, Heritability, Genealogy, Genetic association
Abstract: In the HTML version of this article initially published, the author groups ‘23andMe Research Team’ and ‘Social Science Genetic Association Consortium’ appeared at the end of the author list but should have appeared earlier in the list, after author Nicholas A. Furlotte. The errors have been corrected in the HTML version of the article.
Published: 2019

234. Correction to: A Genetic Investigation of the Well-Being Spectrum

Author: Jacqueline M. Vink, Gonneke Willemsen, M. P. van de Weijer, E.J.C. de Geus, Bart M. L. Baselmans, Meike Bartels, Michel G. Nivard, Abdel Abdellaoui, J-J Hottenga, and Dorret I. Boomsma
Subjects: Netherlands Twin Register (NTR), medicine.medical_specialty, business.industry, Public health, Acknowledgement, Section (typography), Library science, Spectrum (topology), Health psychology, SDG 3 - Good Health and Well-being, Publishing, Well-being, Genetics, medicine, Sociology, business, Developmental Psychopathology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics
Abstract: Item does not contain fulltext In the original version of this article, unfortunately, in the acknowledgement section "National Institutes of Health (NIH, R37 AG033590-08) to J Cacioppo" was omitted. This has been corrected by publishing this erratum. 1 p.
Published: 2019

235. Erratum to 'Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies' [Alzheimer's & Dementia 2018;14:707‐22.]

Author: W. Maier, C M van Duijn, F.A. de Leeuw, Sudha Seshadri, Archana Singh-Manoux, Thomas Hankemeier, Alfredo Ramirez, Carel F.W. Peeters, W.M. van der Flier, Maik Pietzner, T. Haller, K. W. van Dijk, Vincent Chouraki, Gonneke Willemsen, D.I. Boomsma, N. Amin, M. Kivimaki, J. J. M. Van Dongen, Aswin Verhoeven, René Pool, Hans J. Grabe, C.E. Teunissen, Kathrin Budde, Martin J. Shipley, Sarah Egert, C.E.M. van Beijsterveldt, S. J. van der Lee, Johannes Hertel, A. Metspalu, Robert E. Gertzen, Veikko Salomaa, P.E. Slagboom, Siyao Li, A. Teumer, Holger Wagner, Qiong Yang, Ayse Demirkan, Ramachandran S. Vasan, Michael Wagner, Nele Friedrich, Leonie Weinhold, P. Scheltens, Juha Hernesniemi, Ikram, Juho T Tynkkynen, M. Perola, D.M. van Lent, and Karina Fischer
Subjects: Gerontology, Epidemiology, business.industry, Health Policy, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, Dementia, Alzheimer s dementia, ddc:610, Neurology (clinical), Geriatrics and Gerontology, business, Cohort study
Abstract: Erratum to: https://doi.org/10.1016/j.jalz.2019.01.002
Published: 2019

236. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Author: Aravinda Chakravarti, Jennifer E. Huffman, Meixia Ren, Veikko Salomaa, Christopher Newton-Cheh, Johan Sundström, Alan L. James, Joris Deelen, Raha Pazoki, Michela Traglia, Tõnu Esko, Seppo Koskinen, Christopher J. O'Donnell, Csaba P. Kovesdy, Daniel I. Chasman, Paul F. O'Reilly, Roby Joehanes, Paul M. Ridker, G. Abecasis, Lars Lind, Dragana Vuckovic, Yingchang Lu, Antonietta Robino, Anders Hamsten, Muralidharan Sargurupremraj, Caterina Barbieri, Anne U. Jackson, Anna Morgan, Claudia Langenberg, Peter S. Braund, Rainer Rettig, Murielle Bochud, Vilmundur Gudnason, Eleftheria Zeggini, David J. Stott, Joop Jukema, Nick Shrine, Jun Ding, Olle Melander, Massimo Mangino, Borbala Mifsud, Frank H. Collins, Liewald Dcm., Tineka Blake, Peter K. Joshi, Yan V. Sun, Aarno Palotie, Maciej Tomaszewski, Jarvelin M-R., Kati Kristiansson, L. J. Launer, Sara M. Willems, Ian J. Deary, Christophe Tzourio, Alan J. Gow, Caroline Hayward, Guillaume Paré, Christopher Oldmeadow, John M. Starr, Paul Elliott, Morris A. Swertz, C M van Duijn, Sekar Kathiresan, Lorna M. Lopez, Neil R Poulter, Mike A. Nalls, Erik Ingelsson, Eric Boerwinkle, Catharina A. Hartman, Giorgia Girotto, Ben A. Oostra, Markus Perola, Paul Knekt, Lyytikäinen L-P., T.B. Harris, J. C. Bis, Harriëtte Riese, J. Marrugat, Samuli Ripatti, Howson Jmm., Archie Campbell, C M Lindgren, Adam S. Butterworth, Xiuqing Guo, Lin W-Y., Priyanka Nandakumar, David Mosen-Ansorena, Alison Pattie, Marco Brumat, Annette Peters, Georgios Ntritsos, Ivana Kolcic, Alexander Teumer, Ulf Gyllensten, Joanne Knight, Stella Trompet, K. Witkowska, Hottenga J-J., Tim D. Spector, Maris Laan, Vilmantas Giedraitis, Bram P. Prins, Loos Rjf., M. H. de Borst, Antti Jula, Lynda M. Rose, Massimiliano Cocca, Daniela Toniolo, Igor Rudan, P. J. van der Most, Fu Liang Ng, Heather J. Cordell, Walter Palmas, John Danesh, John Attia, Dan E. Arking, Ganesh Chauhan, C Gieger, P. van der Harst, Penninx Bwjh., Kristin L. Ayers, Germaine C. Verwoert, Bruce M. Psaty, Jaspal S. Kooner, Ruifang Li-Gao, Benjamin Lehne, Khaw K-T., Sandosh Padmanabhan, Franco Giulianini, Erwin P. Bottinger, Roberto Elosua, Christopher P. Nelson, Ozren Polasek, D.R. Velez Edwards, Martin Farrall, Ioanna Tzoulaki, Peter Vollenweider, Uwe Völker, Albertine J. Oldehinkel, Åsa Johansson, Helen R. Warren, Evan Tzanis, Albert V. Smith, Hwang S-J., Teresa Ferreira, E.J.C. de Geus, Evangelos Evangelou, Niek Verweij, R. J. Scott, Pekka Jousilahti, Elin Org, Stefan Enroth, Dorret I. Boomsma, Harry Campbell, Andrew D. Johnson, David Conen, James F. Wilson, Edward G. Lakatta, Anuj Goel, Raymond Noordam, Najaf Amin, David P. Strachan, Martin D. Tobin, Francesco Cucca, Doney Asf., Todd L. Edwards, Jerome I. Rotter, Mika Kähönen, Hugh Watkins, Rossella Sorice, John M. C. Connell, David S. Siscovick, Sébastien Thériault, Jian'an Luan, Marty Larson, Philippe Amouyel, A C Morrison, Louise V. Wain, Reedik Mägi, Jonathan Marten, Thibaud Boutin, Nabi Shah, Weihua Zhang, Palmer Cna., Daniela Ruggiero, Zhao J-H., Olli T. Raitakari, Bernard Keavney, Peter S. Sever, Philip S. Tsao, Jie Yao, André G. Uitterlinden, Marina Evangelou, Zoltán Kutalik, Robert A. Scott, Helena Schmidt, J. Tuomilehto, Nilesh J. Samani, Quang Tri Nguyen, John Michael Gaziano, Georg Ehret, Praveen Surendran, Terho Lehtimäki, Mark J. Caulfield, Denis C. Shields, Rick Jansen, Sarin A-P., Alice Stanton, Mattias Frånberg, Cumhur Y Demirkale, Stéphanie Debette, Paolo Gasparini, Ilaria Gandin, Simon Thom, Kent D. Taylor, Andrew D. Morris, Claudia P. Cabrera, Teemu J. Niiranen, Nicholas J. Wareham, Andrew P. Morris, Yasaman Saba, Daniel Levy, Aki S. Havulinna, Kelly Cho, Sarah E. Harris, Li Lin, Janina S. Ried, Michael R. Barnes, Sarah H. Wild, Patricia B. Munroe, Vergnaud A-C., Lorenz Risch, Rona J. Strawbridge, Y. Milaneschi, John C. Chambers, Yong Qian, Cristina Menni, Anubha Mahajan, Peter Almgren, Gary Davies, Jacklyn N. Hellwege, Elizabeth G. Holliday, A. Metspalu, Ilja M. Nolte, Peter J. Munson, He Gao, Marcus Dörr, Cinzia Sala, Peter P. Pramstaller, Teresa Nutile, Wilson Pwf., Gonneke Willemsen, Markku Laakso, Chiara Batini, Harold Snieder, Ibrahim Karaman, Adriana M. Hung, Reinhold Schmidt, R. de Mutsert, Michael Boehnke, Lili Milani, Alan F. Wright, Edith Hofer, Siim Sõber, Ahmad Vaez, Albert Hofman, Oscar H. Franco, Yongmei Liu, Tatijana Zemunik, Kenneth Rice, Veronique Vitart, Marina Ciullo, Niki Dimou, Morris J. Brown, Crysovalanto Mamasoula, A.M. Erzurumluoglu, Andrew A. Hicks, Ayush Giri, Dennis O. Mook-Kanamori, Home Office, UNIVERSITY OF OULU, Commission of the European Communities, Medical Research Council (MRC), Action on Hearing Loss, British Heart Foundation, National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, and UK DRI Ltd
Subjects: Genetics & Heredity, 0301 basic medicine, Netherlands Twin Register (NTR), Science & Technology, computer.internet_protocol, Million Veteran Program, Genome-wide association study, Computational biology, 06 Biological Sciences, Biology, Genetic analysis, 03 medical and health sciences, 030104 developmental biology, Genetics, Genome informatics, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Life Sciences & Biomedicine, computer, 11 Medical and Health Sciences, XML, Developmental Biology
Abstract: In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
Published: 2018

237. Common variants associated with plasma triglycerides and risk for coronary artery disease

Author: Richard S. Cooper, Angela Döring, Cisca Wijmenga, Jerome I. Rotter, Linda S. Adair, Tõnu Esko, Jennifer L. Bragg-Gresham, Danish Saleheen, Narisu Narisu, Xiaohui Li, Kathleen Stirrups, Ulf de Faire, Nicholas G. Martin, Dmitry Shungin, Peter Vollenweider, Yii-Der Ida Chen, Dharambir K. Sanghera, George Dedoussis, Toshiko Tanaka, Manjinder S. Sandhu, Anne U. Jackson, Nancy L. Pedersen, Maria Dimitriou, Shih-Yi Lin, David P. Strachan, Isleifur Olafsson, Ruth J. F. Loos, Kay-Tee Khaw, Antero Kesäniemi, Rainer Rauramaa, Wendy L. McArdle, Gonneke Willemsen, Dena G. Hernandez, May E. Montasser, Amy J. Swift, Colin A. McKenzie, Aaron Isaacs, Latonya F. Been, Leif Groop, Massimo Mangino, Martina Müller-Nurasyid, Karen L. Mohlke, Ci Song, Sailaja Vedantam, Anna-Liisa Hartikainen, Lori L. Bonnycastle, Ilja M. Nolte, Jaakko Kaprio, Anneli Pouta, Unnur Thorsteinsdottir, Paul Elliott, Muredach P. Reilly, Jean Ferrières, Daniel J. Rader, Elizabeth H. Young, Jaspal S. Kooner, Leena Moilanen, Markku Laakso, Albert Hofman, Kelly A. Volcik, Sekar Kathiresan, Tamara B. Harris, Eric Kim, Aimo Ruokonen, Andrea Ganna, Serena Sanna, John J.P. Kastelein, Martha L. Gravito, Ronald M. Krauss, Ken K. Ong, Paul M. Ridker, Kristian Hveem, Ayse Demirkan, Alena Stančáková, Pierre Meneton, Thomas Quertermous, John Danesh, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Christopher J. Groves, Jaakko Tuomilehto, Michael Boehnke, Jose M. Ordovas, Alan B. Feranil, Chao A. Hsiung, Wayne Huey-Herng Sheu, Igor Rudan, Christa Meisinger, Rebecca N. Nsubuga, Bruna Gigante, Inger Njølstad, Göran Hallmans, Aroon D. Hingorani, Jouko Saramies, Deepti Gurdasani, Fernando Rivadeneira, Andres Metspalu, Stephen E. Epstein, Gonçalo R. Abecasis, Braxton D. Mitchell, Devin Absher, Marcus E. Kleber, Sonia Shah, Pierre Fontanillas, Jeffrey R. O'Connell, Louise A. Donnelly, Jing Hua Zhao, Martin L. Buchkovich, Francis S. Collins, Gabrielle Müller, Matti Uusitupa, Evelin Mihailov, Nicholas J. Wareham, Andrew A. Hicks, Dorret I. Boomsma, Harry Campbell, Ellen M. Schmidt, Jaana Lindström, Mark I. McCarthy, Evita G. Van Den Herik, Kirsten Ohm Kyvik, Vilmundur Gudnason, Jackie F. Price, Joel N. Hirschhorn, Winfried März, Aravinda Chakravarti, Pontiano Kaleebu, James F. Wilson, Lindsay L. Waite, Leo-Pekka Lyytikäinen, Sebanti Sengupta, Mika Kivimäki, David Altshuler, Hilma Holm, Rona J. Strawbridge, Harald Grallert, Ramaiah Nagaraja, Laurence Tiret, G. Kees Hovingh, Meena Kumari, Nilesh J. Samani, Daniel F. Freitag, Nelson B. Freimer, Thomas Illig, Panos Deloukas, Bernhard O. Boehm, Nicholas W.J. Wainwright, Mark J. Daly, Mika Kähönen, Michel Burnier, Norman Klopp, L. Adrienne Cupples, Aarno Palotie, Markus Perola, Bamidele O. Tayo, Timo A. Lakka, Matthew Jones, Sarah H. Wild, Patricia B. Munroe, Antti Jula, François Mach, Peter J. Koudstaal, Pirjo Komulainen, Eric Boerwinkle, L. Joost van Pelt, Veikko Salomaa, Ann-Kristin Petersen, Ida Surakka, Andrew Wong, Caroline Hayward, Chi Gao, Cristen J. Willer, Stephen S. Rich, Yi Jen Hung, Peter P. Pramstaller, Diana Kuh, Ron Do, Dominique Arveiler, Mark O. Goodarzi, Ross M. Fraser, Ingrid B. Borecki, Steven C. Hunt, Weihua Zhang, Mary Susan Burnett, Patrik K. E. Magnusson, John C. Chambers, Benjamin M. Neale, Peter Schwarz, Jennifer L. Bolton, Murielle Bochud, Heleen M. den Hertog, Christian Gieger, Cristina Pomilla, Teresa Ferreira, Lars Wallentin, Richa Saxena, André G. Uitterlinden, Kaisa Silander, Ying Wu, Bruce M. Psaty, Jian'an Luan, Hsing-Yi Chang, Jin Chen, Daniel I. Chasman, Ulf Gyllensten, Kari Stefansson, Kauko Heikkilä, Tom Wilsgaard, Alan R. Shuldiner, Carlos Iribarren, Stavroula Kanoni, John Whitfield, Gershim Asiki, Marika Kaakinen, Georg Ehret, Elina Hyppönen, Claudia Langenberg, Gina M. Peloso, Cecilia M. Lindgren, Carlo Sidore, Gudmundur I. Eyjolfsson, Cameron D. Palmer, Jacques S. Beckmann, Hubert Scharnagl, Tanya M. Teslovich, Mary F. Feitosa, Terho Lehtimäki, Steve E. Humphries, Chris Power, Benjamin F. Voight, Stefania Bandinelli, Andrew D. Morris, Gudmar Thorleifsson, Tuomo Nieminen, Tim D. Spector, Paul W. Franks, Themistocles L. Assimes, Pascal Bovet, Luigi Ferrucci, Johannes Kettunen, Inês Barroso, Franklyn I. Bennett, Stefan Gustafsson, Paolo Brambilla, Theodore Papamarkou, Elena Tremoli, Janet Seeley, Alex S. F. Doney, Johanna Kuusisto, Giancarlo Cesana, Bruce H. R. Wolffenbuttel, Lars Lind, Stefan R. Bornstein, Åsa Johansson, Anders Hamsten, Marjo-Riitta Järvelin, Krista Fischer, Agneta Siegbahn, Samia Mora, Erik Ingelsson, Colin N. A. Palmer, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Epidemiology, Surgery, Public Health, Ophthalmology, Neurology, Medical Microbiology & Infectious Diseases, Obstetrics & Gynecology, Internal Medicine, Do, Ron, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Hyppönen, Elina, Kathiresan, Sekar, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Do, R, Willer, C, Schmidt, E, Sengupta, S, Gao, C, Peloso, G, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, M, Mora, S, Beckmann, J, Bragg Gresham, J, Chang, H, Demirkan, A, Den Hertog, H, Donnelly, L, Ehret, G, Esko, T, Feitosa, M, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, R, Freitag, D, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, A, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, M, Li, X, Luan, J, Lyytikäinen, L, Magnusson, P, Mangino, M, Mihailov, E, Montasser, M, Müller Nurasyid, M, Nolte, I, O'Connell, J, Palmer, C, Perola, M, Petersen, A, Sanna, S, Saxena, R, Service, S, Shah, S, Shungin, D, Sidore, C, Song, C, Strawbridge, R, Surakka, I, Tanaka, T, Teslovich, T, Thorleifsson, G, Van den Herik, E, Voight, B, Volcik, K, Waite, L, Wong, A, Wu, Y, Zhang, W, Absher, D, Asiki, G, Barroso, I, Been, L, Bolton, J, Bonnycastle, L, Brambilla, P, Burnett, M, Cesana, G, Dimitriou, M, Doney, A, Döring, A, Elliott, P, Epstein, S, Eyjolfsson, G, Gigante, B, Goodarzi, M, Grallert, H, Gravito, M, Groves, C, Hallmans, G, Hartikainen, A, Hayward, C, Hernandez, D, Hicks, A, Holm, H, Hung, Y, Illig, T, Jones, M, Kaleebu, P, Kastelein, J, Khaw, K, Kim, E, Klopp, N, Komulainen, P, Kumari, M, Langenberg, C, Lehtimäki, T, Lin, S, Lindström, J, Loos, R, Mach, F, Mcardle, W, Meisinger, C, Mitchell, B, Müller, G, Nagaraja, R, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Ong, K, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Rader, D, Reilly, M, Ridker, P, Rivadeneira, F, Rudan, I, Ruokonen, A, Samani, N, Scharnagl, H, Seeley, J, Silander, K, Stančáková, A, Stirrups, K, Swift, A, Tiret, L, Uitterlinden, A, van Pelt, L, Vedantam, S, Wainwright, N, Wijmenga, C, Wild, S, Willemsen, G, Wilsgaard, T, Wilson, J, Young, E, Zhao, J, Adair, L, Arveiler, D, Assimes, T, Bandinelli, S, Bennett, F, Bochud, M, Boehm, B, Boomsma, D, Borecki, I, Bornstein, S, Bovet, P, Burnier, M, Campbell, H, Chakravarti, A, Chambers, J, Chen, Y, Collins, F, Cooper, R, Danesh, J, Dedoussis, G, de Faire, U, Feranil, A, Ferrières, J, Ferrucci, L, Freimer, N, Gieger, C, Groop, L, Gudnason, V, Gyllensten, U, Hamsten, A, Harris, T, Hingorani, A, Hirschhorn, J, Hofman, A, Hovingh, G, Hsiung, C, Humphries, S, Hunt, S, Hveem, K, Iribarren, C, Järvelin, M, Jula, A, Kähönen, M, Kaprio, J, Kesäniemi, A, Kivimaki, M, Kooner, J, Koudstaal, P, Krauss, R, Kuh, D, Kuusisto, J, Kyvik, K, Laakso, M, Lakka, T, Lind, L, Lindgren, C, Martin, N, März, W, Mccarthy, M, Mckenzie, C, Meneton, P, Metspalu, A, Moilanen, L, Morris, A, Munroe, P, Njølstad, I, Pedersen, N, Power, C, Pramstaller, P, Price, J, Psaty, B, Quertermous, T, Rauramaa, R, Saleheen, D, Salomaa, V, Sanghera, D, Saramies, J, Schwarz, P, Sheu, W, Shuldiner, A, Siegbahn, A, Spector, T, Stefansson, K, Strachan, D, Tayo, B, Tremoli, E, Tuomilehto, J, Uusitupa, M, van Duijn, C, Vollenweider, P, Wallentin, L, Wareham, N, Whitfield, J, Wolffenbuttel, B, Altshuler, D, Ordovas, J, Boerwinkle, E, Thorsteinsdottir, U, Chasman, D, Rotter, J, Franks, P, Ripatti, S, Cupples, L, Sandhu, M, Rich, S, Boehnke, M, Deloukas, P, Mohlke, K, Ingelsson, E, Abecasis, G, Daly, M, Neale, B, and Kathiresan, S
Subjects: Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Heart disease, Genome-wide association study, Coronary Artery Disease, 030204 cardiovascular system & hematology, ISCHEMIC-HEART-DISEASE, Triglyceride, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Polymorphism (computer science), Risk Factors, High-density-lipoprotein, Genetic epidemiology, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Cholesterol, HDL/blood, Cholesterol levels, Loci, Contribute, Single Nucleotide, LDL/blood, Triglycerides/blood, Cholesterol, Cholesterol, LDL/blood, HDL/blood, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Human, medicine.medical_specialty, TYPE-2 DIABETES-MELLITUS, Biology, Polymorphism, Single Nucleotide, Article, HIGH-DENSITY-LIPOPROTEIN ISCHEMIC-HEART-DISEASE TYPE-2 DIABETES-MELLITUS MENDELIAN RANDOMIZATION CARDIOVASCULAR-DISEASE GENETIC EPIDEMIOLOGY CHOLESTEROL LEVELS LOCI CONTRIBUTE THERAPY, 03 medical and health sciences, Coronary Artery Disease/blood, SDG 3 - Good Health and Well-being, Cardiovascular-disease, Internal medicine, Mendelian randomization, Genetics, medicine, Humans, Polymorphism, plasma, Triglycerides, 030304 developmental biology, Science & Technology, Risk Factor, Cholesterol, HDL, Biological Transport, Cholesterol, LDL, 06 Biological Sciences, medicine.disease, Heart-disease, lipoproteins, Endocrinology, chemistry, Therapy, Developmental Biology
Abstract: Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10 -8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. © 2013 Nature America, Inc. All rights reserved.
Published: 2013

238. Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Author: Aaron Isaacs, Cornelia M. van Duijn, Claire J. Steves, Jacqueline M. Vink, Christopher P. Nelson, Marian Beekman, Linda Broer, Anton J. M. de Craen, Joris Deelen, Gonneke Willemsen, Tim D. Spector, Nicholas G. Martin, Nilesh J. Samani, P. Eline Slagboom, Veryan Codd, Anjali K. Henders, Massimo Mangino, Mary K. Matthews, Dorret I. Boomsma, Alireza Moayyeri, Margie Wright, Najaf Amin, Dale R. Nyholt, Eco J. C. de Geus, Grant W. Montgomery, Ben A. Oostra, Eva Albrecht, Epidemiology, Clinical Genetics, Hematology, Biological Psychology, and EMGO+ - Mental Health
Subjects: Netherlands Twin Register (NTR), Male, Non-Mendelian inheritance, medicine.risk_factor, Inheritance Patterns, heritability, 0302 clinical medicine, telomere length, 80 and over, Telomere Length, Heritability, Paternal Age Effect, Telomere Shortening, Genetics (clinical), Genetics, Aged, 80 and over, 0303 health sciences, education.field_of_study, Age Factors, Telomere, Middle Aged, Pedigree, Telomere Shortening/genetics, Female, Twins/genetics, Adult, Adolescent, Offspring, Population, Biology, Article, Paternal Age, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Paternal age effect, education, 030304 developmental biology, Aged, Telomere/genetics, Case-control study, paternal age effect, Twin study, Case-Control Studies, 030217 neurology & neurosurgery, Demography
Abstract: Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64-0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother-offspring (r=0.42; P-value=3.60 × 10(-61)) than father-offspring correlation (r=0.33; P-value=7.01 × 10(-5)), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10(-5)). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10(-30)) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10(-23)) than in younger pairs (mean age
Published: 2013

239. Population structure, migration, and diversifying selection in the Netherlands

Author: Xiangjun Xiao, James J. Hudziak, Eco J. C. de Geus, Gareth E. Davies, Jouke-Jan Hottenga, Paul Scheet, Michel G. Nivard, Yueshan Hu, Brenda W.J.H. Penninx, Peter de Knijff, Abdel Abdellaoui, Andrew Brooks, Gonneke Willemsen, Dorret I. Boomsma, Toos C. E. M. van Beijsterveldt, Erik A. Ehli, Patrick F. Sullivan, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Mental health
Subjects: Netherlands Twin Register (NTR), Linkage disequilibrium, Human Migration, Population, Single-nucleotide polymorphism, Genome-wide association study, Biology, migration, Population stratification, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Genetic variation, Confidence Intervals, Genetics, Humans, Selection, Genetic, 10. No inequality, education, Genetics (clinical), Selection (genetic algorithm), Netherlands, 030304 developmental biology, Genetic association, Principal Component Analysis, PCA, 0303 health sciences, education.field_of_study, Geography, Genome, Human, Genetic Variation, diversifying selection, population structure, Genetics, Population, Haplotypes, linkage disequilibrium, 030217 neurology & neurosurgery, Genealogy and Heraldry, Genome-Wide Association Study
Abstract: Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North-South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs-the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. © 2013 Macmillan Publishers Limited.
Published: 2013

240. Discovery and refinement of loci associated with lipid levels

Author: Benjamin F. Voight, Stefania Bandinelli, Pascal Bovet, Latonya F. Been, Ci Song, Luigi Ferrucci, Johannes Kettunen, Andrew D. Morris, Mary Susan Burnett, Ronald M. Krauss, Igor Rudan, Heleen M. den Hertog, Stavroula Kanoni, G. Kees Hovingh, Elina Hyppönen, Kauko Heikkilä, Richard S. Cooper, Daniel I. Chasman, Bruna Gigante, Stefan Gustafsson, Jian'an Luan, Sarah H. Wild, Patricia B. Munroe, Göran Hallmans, Jeffrey R. O'Connell, Danish Saleheen, Aarno Palotie, Leena Moilanen, Jerome I. Rotter, Caroline Hayward, Jennifer L. Bragg-Gresham, Nicholas G. Martin, Claudia Langenberg, George Dedoussis, Carlo Sidore, Ulf Gyllensten, Marika Kaakinen, Jing Hua Zhao, Aimo Ruokonen, Diana Kuh, Maria Dimitriou, Shih-Yi Lin, Gina M. Peloso, Marcus E. Kleber, Christopher J. Groves, Alena Stančáková, Michel Burnier, Patrik K. E. Magnusson, John C. Chambers, Giancarlo Cesana, Francis S. Collins, Gabrielle Müller, Angela Döring, Colin A. McKenzie, Paul Elliott, Lars Lind, Vilmundur Gudnason, Dharambir K. Sanghera, Jean Ferrières, Toshiko Tanaka, Stefan R. Bornstein, Gershim Asiki, Jacques S. Beckmann, Anneli Pouta, Timo A. Lakka, Daniel J. Rader, Elizabeth H. Young, Kelly A. Volcik, Dena G. Hernandez, Ann-Kristin Petersen, Kristian Hveem, Amy J. Swift, Murielle Bochud, Pierre Meneton, Paul M. Ridker, Kathleen Stirrups, Stephen S. Rich, Isleifur Olafsson, Ruth J. F. Loos, Serena Sanna, Markus Perola, Meena Kumari, Cameron D. Palmer, Carlos Iribarren, Nancy L. Pedersen, Mark O. Goodarzi, Panos Deloukas, Norman Klopp, Cristina Pomilla, Stephen E. Epstein, Antti Jula, Themistocles L. Assimes, Martina Müller-Nurasyid, Marjo-Riitta Järvelin, Chao A. Hsiung, Sonia Shah, Christian Gieger, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Nicholas J. Wareham, Krista Fischer, Wendy L. McArdle, Linda S. Adair, Kay-Tee Khaw, Bruce M. Psaty, André G. Uitterlinden, Aaron Isaacs, Tõnu Esko, Jennifer L. Bolton, Rebecca N. Nsubuga, Eric Boerwinkle, L. Joost van Pelt, Jouko Saramies, François Mach, Pierre Fontanillas, Teresa Ferreira, Lars Wallentin, Michael Boehnke, Christa Meisinger, Wayne Huey-Herng Sheu, Gonçalo R. Abecasis, Inês Barroso, Franklyn I. Bennett, Dmitry Shungin, Jaakko Kaprio, Kirsten Ohm Kyvik, Deepti Gurdasani, Anne U. Jackson, Paolo Brambilla, Georg Ehret, Cecilia M. Lindgren, Fernando Rivadeneira, Theodore Papamarkou, Jaakko Tuomilehto, Cristen J. Willer, Martin L. Buchkovich, Antero Kesäniemi, Hubert Scharnagl, Xiaohui Li, Elena Tremoli, Nelson B. Freimer, Mika Kähönen, Ron Do, Karen L. Mohlke, Thomas Illig, Gudmar Thorleifsson, Peter J. Koudstaal, Andres Metspalu, Ulf de Faire, Dominique Arveiler, Harald Grallert, Jaana Lindström, Laurence Tiret, Jaspal S. Kooner, Braxton D. Mitchell, Sebanti Sengupta, Gonneke Willemsen, Anna-Liisa Hartikainen, Terho Lehtimäki, Steve E. Humphries, Peter Schwarz, Dorret I. Boomsma, Harry Campbell, Ellen M. Schmidt, Tom Wilsgaard, Janet Seeley, Alex S. F. Doney, Alan R. Shuldiner, John Whitfield, Markku Laakso, Peter Vollenweider, Gudmundur I. Eyjolfsson, Winfried März, Mika Kivimäki, Ying Wu, Johanna Kuusisto, Andrew A. Hicks, Bruce H. R. Wolffenbuttel, May E. Montasser, Bamidele O. Tayo, Unnur Thorsteinsdottir, Muredach P. Reilly, Leo-Pekka Lyytikäinen, Eric Kim, John Danesh, Ida Surakka, Åsa Johansson, Anders Hamsten, Thomas Quertermous, Hsing-Yi Chang, Jin Chen, Agneta Siegbahn, Narisu Narisu, Samia Mora, Erik Ingelsson, Colin N. A. Palmer, Sekar Kathiresan, Manjinder S. Sandhu, Leif Groop, Jose M. Ordovas, Alan B. Feranil, Evelin Mihailov, Hilma Holm, Pontiano Kaleebu, Lindsay L. Waite, Ramaiah Nagaraja, Andrew Wong, Rona J. Strawbridge, David P. Strachan, Yii-Der Ida Chen, Tamara B. Harris, Jackie F. Price, Aravinda Chakravarti, Veikko Salomaa, Sailaja Vedantam, Albert Hofman, Devin Absher, Ross M. Fraser, Kaisa Silander, Pirjo Komulainen, Yi Jen Hung, Peter P. Pramstaller, Kari Stefansson, Aroon D. Hingorani, Tanya M. Teslovich, Matti Uusitupa, L. Adrienne Cupples, Cisca Wijmenga, Lori L. Bonnycastle, Ilja M. Nolte, Andrea Ganna, Ken K. Ong, Inger Njølstad, Bernhard O. Boehm, Nicholas W.J. Wainwright, Richa Saxena, Rainer Rauramaa, Louise A. Donnelly, James F. Wilson, Matthew Jones, Ingrid B. Borecki, Steven C. Hunt, Weihua Zhang, Massimo Mangino, John J.P. Kastelein, Martha L. Gravito, Mark I. McCarthy, Evita G. Van Den Herik, Joel N. Hirschhorn, Nilesh J. Samani, Daniel F. Freitag, Ayse Demirkan, Mary F. Feitosa, Tuomo Nieminen, Tim D. Spector, Paul W. Franks, Chris Power, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Willer, C, Schmidt, E, Sengupta, S, Peloso, G, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, M, Mora, S, Beckmann, J, Bragg Gresham, J, Chang, H, Demirkan, A, Den Hertog, H, Do, R, Donnelly, L, Ehret, G, Esko, T, Feitosa, M, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, R, Freitag, D, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, A, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, M, Li, X, Luan, J, Lyytikäinen, L, Magnusson, P, Mangino, M, Mihailov, E, Montasser, M, Müller Nurasyid, M, Nolte, I, O'Connell, J, Palmer, C, Perola, M, Petersen, A, Sanna, S, Saxena, R, Service, S, Shah, S, Shungin, D, Sidore, C, Song, C, Strawbridge, R, Surakka, I, Tanaka, T, Teslovich, T, Thorleifsson, G, Van den Herik, E, Voight, B, Volcik, K, Waite, L, Wong, A, Wu, Y, Zhang, W, Absher, D, Asiki, G, Barroso, I, Been, L, Bolton, J, Bonnycastle, L, Brambilla, P, Burnett, M, Cesana, G, Dimitriou, M, Doney, A, Döring, A, Elliott, P, Epstein, S, Eyjolfsson, G, Gigante, B, Goodarzi, M, Grallert, H, Gravito, M, Groves, C, Hallmans, G, Hartikainen, A, Hayward, C, Hernandez, D, Hicks, A, Holm, H, Hung, Y, Illig, T, Jones, M, Kaleebu, P, Kastelein, J, Khaw, K, Kim, E, Klopp, N, Komulainen, P, Kumari, M, Langenberg, C, Lehtimäki, T, Lin, S, Lindström, J, Loos, R, Mach, F, Mcardle, W, Meisinger, C, Mitchell, B, Müller, G, Nagaraja, R, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Ong, K, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Rader, D, Reilly, M, Ridker, P, Rivadeneira, F, Rudan, I, Ruokonen, A, Samani, N, Scharnagl, H, Seeley, J, Silander, K, Stancáková, A, Stirrups, K, Swift, A, Tiret, L, Uitterlinden, A, van Pelt, L, Vedantam, S, Wainwright, N, Wijmenga, C, Wild, S, Willemsen, G, Wilsgaard, T, Wilson, J, Young, E, Zhao, J, Adair, L, Arveiler, D, Assimes, T, Bandinelli, S, Bennett, F, Bochud, M, Boehm, B, Boomsma, D, Borecki, I, Bornstein, S, Bovet, P, Burnier, M, Campbell, H, Chakravarti, A, Chambers, J, Chen, Y, Collins, F, Cooper, R, Danesh, J, Dedoussis, G, de Faire, U, Feranil, A, Ferrières, J, Ferrucci, L, Freimer, N, Gieger, C, Groop, L, Gudnason, V, Gyllensten, U, Hamsten, A, Harris, T, Hingorani, A, Hirschhorn, J, Hofman, A, Hovingh, G, Hsiung, C, Humphries, S, Hunt, S, Hveem, K, Iribarren, C, Järvelin, M, Jula, A, Kähönen, M, Kaprio, J, Kesäniemi, A, Kivimaki, M, Kooner, J, Koudstaal, P, Krauss, R, Kuh, D, Kuusisto, J, Kyvik, K, Laakso, M, Lakka, T, Lind, L, Lindgren, C, Martin, N, März, W, Mccarthy, M, Mckenzie, C, Meneton, P, Metspalu, A, Moilanen, L, Morris, A, Munroe, P, Njølstad, I, Pedersen, N, Power, C, Pramstaller, P, Price, J, Psaty, B, Quertermous, T, Rauramaa, R, Saleheen, D, Salomaa, V, Sanghera, D, Saramies, J, Schwarz, P, Sheu, W, Shuldiner, A, Siegbahn, A, Spector, T, Stefansson, K, Strachan, D, Tayo, B, Tremoli, E, Tuomilehto, J, Uusitupa, M, van Duijn, C, Vollenweider, P, Wallentin, L, Wareham, N, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Boerwinkle, E, Thorsteinsdottir, U, Chasman, D, Rotter, J, Franks, P, Ripatti, S, Cupples, L, Sandhu, M, Rich, S, Boehnke, M, Deloukas, P, Kathiresan, S, Mohlke, K, Ingelsson, E, Abecasis, G, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Ehret, Georg Benedikt, Mach, François, Epidemiology, Surgery, Public Health, Ophthalmology, Neurology, Medical Microbiology & Infectious Diseases, Obstetrics & Gynecology, Internal Medicine, National Institute for Health Research, Global Lipids Genetics Consortium, Willer, Cristen, Sengupta, Sebanti, Peloso, Gina, Hypponen, Elina Tuulikki, and Abecasis, Gonçalo R
Subjects: Netherlands Twin Register (NTR), HOMEOSTASIS, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Blood lipids, Genome-wide association study, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Triglyceride, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, European Continental Ancestry Group/genetics, triglycerides, IDENTIFIES 13, 11 Medical and Health Sciences, African Continental Ancestry Group, 2. Zero hunger, Genetics, Genetics & Heredity, ddc:616, RISK, 0303 health sciences, Cholesterol, HDL/blood, PLASMA, Global Lipids Genetics Consortium, Cholesterol, HDL/blood/genetics, Lipid, Lipids, 3. Good health, LDL/blood, Triglycerides/blood, Lipids/blood/genetics, Cholesterol, Cholesterol, LDL/blood, DENSITY-LIPOPROTEIN CHOLESTEROL, CARDIOVASCULAR-DISEASE, HDL/blood, CORONARY-ARTERY-DISEASE, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, coronary artery disease, TRAITS, Human, Coronary Artery Disease/blood/genetics, Asian Continental Ancestry Group, Genotype, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Black People, HEART-DISEASE, Biology, Article, White People, lipids, 03 medical and health sciences, Coronary Artery Disease/blood, CORONARY-ARTERY-DISEASE DENSITY-LIPOPROTEIN CHOLESTEROL GENOME-WIDE ASSOCIATION HEART-DISEASE CARDIOVASCULAR-DISEASE SUSCEPTIBILITY LOCI IDENTIFIES 13 RISK GENE METAANALYSIS, Triglycerides/blood/genetics, Asian People, SDG 3 - Good Health and Well-being, Mendelian randomization, medicine, Humans, Asian Continental Ancestry Group/genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Genotyping, Triglycerides, METAANALYSIS, 030304 developmental biology, Science & Technology, Lipids/blood, Cholesterol, HDL, cholesterol, African Continental Ancestry Group/genetics, Cholesterol, LDL, 06 Biological Sciences, medicine.disease, GENE, chemistry, Cholesterol, LDL/blood/genetics, Lipoprotein, Developmental Biology, Genome-Wide Association Study
Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10 -8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research. © 2013 Nature America, Inc. All rights reserved.
Published: 2013
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241. The Adult Netherlands Twin Register: Twenty-Five Years of Survey and Biological Data Collection

Author: Hamdi Mbarek, P. Eline Slagboom, Abdel Abdellaoui, H. Eka D. Suchiman, Mathijs Kattenberg, René Pool, Marleen H. M. de Moor, Harmen H.M. Draisma, Jacqueline M. Vink, Dorret I. Boomsma, Lot M. Geels, Melanie Neijts, Jenny van Dongen, Natascha Stroo, Eco J. C. de Geus, Lannie Ligthart, Jenny H. D. A. van Beek, René van Lien, Cornelis Kluft, Gonneke Willemsen, Anouk den Braber, Dennis van 't Ent, Pediatric surgery, Neurology, Amsterdam Neuroscience - Neurodegeneration, VU University medical center, Epidemiology and Data Science, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Neuroscience Campus Amsterdam - Brain Imaging Technology, Biological Psychology, EMGO+ - Mental Health, Clinical Child and Family Studies, Molecular and Computational Toxicology, and Internal Medicine
Subjects: Gerontology, Adult, Male, Netherlands Twin Register (NTR), Biomedical Research, Adolescent, media_common.quotation_subject, Twins, Genome-wide association study, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Diseases in Twins, Medicine, Personality, Humans, Genetic Predisposition to Disease, Longitudinal Studies, Registries, Young adult, Genetics (clinical), 030304 developmental biology, media_common, Biological Specimen Banks, Netherlands, 0303 health sciences, business.industry, gene finding, Obstetrics and Gynecology, longitudinal surveys, DNA, twin family studies, Biobank, Mental health, Twin study, biobank, Pediatrics, Perinatology and Child Health, Female, Gene-Environment Interaction, business, Neurocognitive, 030217 neurology & neurosurgery, Record linkage, Genome-Wide Association Study
Abstract: Over the past 25 years, the Adult Netherlands Twin Register (ANTR) has collected a wealth of information on physical and mental health, lifestyle, and personality in adolescents and adults. This article provides an overview of the sources of information available, the main research findings, and an outlook for the future. Between 1991 and 2012, longitudinal surveys were completed by twins, their parents, siblings, spouses, and offspring. Data are available for 33,957 participants, with most individuals having completed two or more surveys. Smaller projects provided in-depth phenotyping, including measurements of the autonomic nervous system, neurocognitive function, and brain imaging. For 46% of the ANTR participants, DNA samples are available and whole genome scans have been obtained in more than 11,000 individuals. These data have resulted in numerous studies on heritability, gene x environment interactions, and causality, as well as gene finding studies. In the future, these studies will continue with collection of additional phenotypes, such as metabolomic and telomere length data, and detailed genetic information provided by DNA and RNA sequencing. Record linkage to national registers will allow the study of morbidity and mortality, thus providing insight into the development of health, lifestyle, and behavior across the lifespan. Copyright © The Authors 2013.
Published: 2013

242. Association Between Autozygosity and Major Depression: Stratification Due to Religious Assortment

Author: Johannes H. Smit, Gonneke Willemsen, Erik A. Ehli, Gareth E. Davies, Dorret I. Boomsma, Brenda W.J.H. Penninx, James J. Hudziak, Xiangjun Xiao, Andrew Brooks, Meike Bartels, Patrick F. Sullivan, Dirk J.A. Smit, Eco J. C. de Geus, Paul Scheet, Abdel Abdellaoui, Jouke-Jan Hottenga, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Epidemiology and Data Science, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, and Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease
Subjects: Netherlands Twin Register (NTR), Secularism, Population, Autozygosity, Consanguinity, Major depressive disorder, Runs of Homozygosity, Population stratification, Runs of homozygosity, Article, 03 medical and health sciences, Assortative mating, 0302 clinical medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Netherlands, 030304 developmental biology, Genetic association, Depressive Disorder, Major, 0303 health sciences, education.field_of_study, Homozygote, fungi, Genetic Variation, food and beverages, medicine.disease, Religion, Genetics, Population, Psychology, Inbreeding, Social psychology, 030217 neurology & neurosurgery, Demography
Abstract: The effects of inbreeding on the health of offspring can be studied by measuring genome-wide autozygosity as the proportion of the genome in runs of homozygosity (F roh) and relate F roh to outcomes such as psychiatric phenotypes. To successfully conduct these studies, the main patterns of variation for genome-wide autozygosity between and within populations should be well understood and accounted for. Within population variation was investigated in the Dutch population by comparing autozygosity between religious and non-religious groups. The Netherlands have a history of societal segregation and assortment based on religious affiliation, which may have increased parental relatedness within religious groups. Religion has been associated with several psychiatric phenotypes, such as major depressive disorder (MDD). We investigated whether there is an association between autozygosity and MDD, and the extent to which this association can be explained by religious affiliation. All F roh analyses included adjustment for ancestry-informative principal components (PCs) and geographic factors. Religious affiliation was significantly associated with autozygosity, showing that F roh has the ability to capture within population differences that are not captured by ancestry-informative PCs or geographic factors. The non-religious group had significantly lower F roh values and significantly more MDD cases, leading to a nominally significant negative association between autozygosity and depression. After accounting for religious affiliation, MDD was not associated with F roh, indicating that the relation between MDD and inbreeding was due to stratification. This study shows how past religious assortment and recent secularization can have genetic consequences in a relatively small country. This warrants accounting for the historical social context and its effects on genetic variation in association studies on psychiatric and other related traits.
Published: 2013

243. Aging as Accelerated Accumulation of Somatic Variants: Whole-Genome Sequencing of Centenarian and Middle-Aged Monozygotic Twin Pairs

Author: Gert-Jan B. van Ommen, Joris Deelen, Kai Ye, Jeanine J. Houwing-Duistermaat, Rudi G. J. Westendorp, David R. Cox, P. Eline Slagboom, Dorret I. Boomsma, Seyed Yahya Anvar, Eric-Wubbo Lameijer, Zemin Ning, Quan Long, Jeroen F. J. Laros, Ruud van der Breggen, Steven J. Pitts, Keiran Raine, Yanju Zhang, Victor Guryev, Peter A C 't Hoen, Gonneke Willemsen, Shobha Potluri, Dennis Kremer, Ben Blackburne, David T. Jones, Johan T. den Dunnen, Matthijs Moed, Erik B. van den Akker, Marian Beekman, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Stem Cell Aging Leukemia and Lymphoma (SALL), and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Adult, Male, Netherlands Twin Register (NTR), Aging, Somatic cell, READS, twin discordances, Monozygotic twin, Genomics, Biology, Genome, 03 medical and health sciences, 0302 clinical medicine, human genome, Humans, Genetics (clinical), 030304 developmental biology, Genetics, Whole genome sequencing, Aged, 80 and over, 0303 health sciences, Blood Cells, Genome, Human, next gen sequencing, Intron, Obstetrics and Gynecology, High-Throughput Nucleotide Sequencing, Ion semiconductor sequencing, Twins, Monozygotic, Middle Aged, DISCORDANT, Pediatrics, Perinatology and Child Health, Mutation, somatic mutations, Human genome, Female, 030217 neurology & neurosurgery
Abstract: It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins. © The Authors 2013.
Published: 2013
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244. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author: Niina Eklund, Robert C. Kaplan, Niek Verweij, Marcus Richards, Nancy L. Heard-Costa, Angelo Tremblay, Lu Qi, Andres Metspalu, Mark A. Sarzynski, Charleston W. K. Chiang, Tõnu Esko, Jaana Lindström, Pirro G. Hysi, Torben Hansen, James F. Wilson, Serena Sanna, Marie-Claude Vohl, Lynda M. Rose, Daniele Cusi, Megan T. Smith, Anne U. Jackson, Jing Hua Zhao, Anubha Mahajan, Nele Friedrich, Marcel Bruinenberg, Lori L. Bonnycastle, Ilja M. Nolte, Timothy M. Frayling, Weihua Zhang, Lavinia Paternoster, Jenny van Dongen, Torben Jørgensen, Aarno Palotie, Jana V. van Vliet-Ostaptchouk, Martin Farrall, Konstantin Strauch, Jan Smit, Zoltán Kutalik, Anne E. Justice, Elisabeth Widen, Tuomo Rankinen, Timo A. Lakka, Maria Dimitriou, Louis Pérusse, Peter J. van der Most, Yun Ju Sung, George Dedoussis, Caroline Hayward, Tom Wilsgaard, Peter P. Pramstaller, Maria Karaleftheri, Seppo Koskinen, Clive Osmond, Panos Deloukas, David J. Hunter, Kathleen Stirrups, Nicola Glorioso, Andrew T. Hattersley, Hugh Watkins, Sven Bergmann, Eric Boerwinkle, Catharina A. Hartman, Anke Tönjes, Daniel I. Chasman, May E. Montasser, Alan James, Ben A. Oostra, Nigel W. Rayner, Massimo Mangino, Ron T. Gansevoort, Cristina Barlassina, Johanna Kuusisto, Andrew A. Hicks, Roberto Lorbeer, Tomi Laitinen, Narisu Narisu, Stefan R. Bornstein, Gemma Cadby, Johan G. Eriksson, Gudmar Thorleifsson, Erika Salvi, Jari Lahti, Cornelia M. van Duijn, Janina M. Jeff, Heather M. Stringham, Bruce M. Psaty, Thomas W. Winkler, Paul M. Ridker, Unnur Thorsteinsdottir, Lyle J. Palmer, Alexander Teumer, Jürgen Gräßler, Allan Linneberg, Francesca D'Avila, Markku Heliövaara, Harald Grallert, Ivana Kolcic, Kari E. North, Eleftheria Zeggini, James S. Pankow, Alena Standáková, Marjo-Riitta Järvelin, Ozren Polasek, Krista Fischer, Valeriya Lyssenko, Thorkild I. A. Sørensen, André G. Uitterlinden, Stavroula Kanoni, Caroline S. Fox, Sophie R. Wang, Treva Rice, Maria Grazia Pilia, Olli T. Raitakari, Claudia Langenberg, Thomas Sparsø, Emmanouil Tsafantakis, Irene Pichler, Kathy Ryan, Eero Jokinen, Mika Kähönen, Leif Groop, Irene Mateo Leach, Gabriele Müller, Annette Peters, Peter Vollenweider, Oddgeir L. Holmen, David Schlessinger, Paul Knekt, M. Carola Zillikens, Evelin Mihailov, Erkki Vartiainen, Nicholas J. Wareham, Francis S. Collins, Sirkka Keinänen-Kiukaanniemi, Mark I. McCarthy, Joel N. Hirschhorn, Frank B. Hu, Janina S. Ried, Valgerdur Steinthorsdottir, Shapour Jalilzadeh, Peter Kovacs, Anuj Goel, Pim van der Harst, Peter Schwarz, Mathias Gorski, Jorma Viikari, Uwe Völker, Cecilia M. Lindgren, Theodosios Kyriakou, Morris A. Swertz, Inga Prokopenko, Ken K. Ong, Leena Kinnunen, Markus Perola, Kristian Hveem, Matthias Blüher, Rebecca Mills, Albertine J. Oldehinkel, Anders Hamsten, Mattias Lorentzon, Joel Eriksson, Karen L. Mohlke, Rasmus Ribel-Madsen, Pekka Jousilahti, Paolo Manunta, Eva Albrecht, Jeffrey R. O'Connell, Wendy L. McArdle, Amy J. Swift, Dorret I. Boomsma, Harry Campbell, Fracensco Cucca, Aaron Isaacs, Andrew Wong, Georg Homuth, Laura M. Yerges-Armstrong, Carolina Medina-Gomez, Kay-Tee Khaw, Claes Ohlsson, Claude Bouchard, John Blangero, Aliki-Eleni Farmaki, Lorraine Southam, Anette P. Gjesing, Traci M. Bartz, Dabeeru C. Rao, Andrew P. Morris, David P. Strachan, Nita G. Forouhi, Eco J. C. de Geus, Jaakko Tuomilehto, Antti Jula, Ryan W. Walker, Mary F. Feitosa, Reedik Mägi, Aki S. Havulinna, Inger Njølstad, Alan R. Shudiner, Jennifer E. Huffman, Peter Lichtner, Richard N. Bergman, Mariaelisa Graff, Diana Kuh, Tim D. Spector, Robert Luben, Veikko Salomaa, Christian Gieger, Jaspal S. Kooner, Teresa Ferreira, Jennifer L. Bragg-Gresham, Sylvain Sebert, Terho Lehtimäki, Heikki A. Koistinen, Alexandra M. Lewin, Alexessander Couto Alves, Peter S. Chines, Lise Lotte N. Husemoen, Salome Scholtens, Yii-Der Ida Chen, Kati Kristiansson, Barbara McKnight, Sara M. Willems, Rainer Rauramaa, Satu Männistö, Stephan J. L. Bakker, Angela Döring, Audrey Y. Chu, Niels Grarup, Matti Uusitupa, Hannu Puolijoki, L. Adrienne Cupples, Veronique Vitart, Marie Neergaard Harder, Jouke-Jan Hottenga, Kari Stefansson, Alan F. Wright, Igor Rudan, Keri L. Monda, Jian'an Luan, Robert A. Scott, Albert Hofman, Tarunveer S. Ahluwalia, Liesbeth Vandenput, Maija Hassinen, Sarah H. Wild, Iris M. Heid, Brenda W.J.H. Penninx, John C. Chambers, Claire Bellis, Nicholas D. Hastie, Ruth J. F. Loos, Martina Müller-Nurasyid, Johanne Marie Justesen, Gérard Waeber, Jennie Hui, Gonçalo R. Abecasis, Ishminder K. Kooner, Harold Snieder, Judith M. Vonk, Ioanna Tachmazidou, Ronald P. Stolk, Michael Stumvoll, Till Ittermann, Oluf Pedersen, Ingrid B. Borecki, Gonneke Willemsen, Jagvir Grewal, Markku Laakso, Arthur W. Musk, Eero Kajantie, Hans L. Hillege, Michael Boehnke, Cristina Venturini, Lili Milani, John Beilby, Fernando Rivadeneira, Biochemie, RS: FHML MaCSBio, RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, Goel, Anuj [0000-0003-2307-4021], Jackson, Anne U [0000-0002-9672-2547], Kristiansson, Kati [0000-0003-4688-107X], Medina-Gomez, Carolina [0000-0001-7999-5538], Nolte, Ilja M [0000-0001-5047-4077], Prokopenko, Inga [0000-0003-1624-7457], Teumer, Alexander [0000-0002-8309-094X], Wong, Andrew [0000-0003-2079-4779], Beilby, John [0000-0002-4915-2254], Bergmann, Sven [0000-0002-6785-9034], Strachan, David P [0000-0001-7854-1366], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Energy & Sustainability Programme, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Children's Hospital, Lastentautien yksikkö, Clinicum, Institute for Molecular Medicine Finland, Behavioural Sciences, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Department of Medicine, Endokrinologian yksikkö, Aarno Palotie / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, University of Helsinki, Leif Groop Research Group, Quantitative Genetics, HUS Children and Adolescents, Developmental Psychology Research Group, Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, School of Medicine / Clinical Medicine, School of Medicine / Biomedicine,School of Medicine / Clinical Nutrition, Ried, Janina S., Jeff, Janina M., Chu, Audrey Y., Bragg Gresham, Jennifer L., Van Dongen, Jenny, Huffman, Jennifer E., Ahluwalia, Tarunveer S., Cadby, Gemma, Eklund, Niina, Eriksson, Joel, Esko, Toñu, Feitosa, Mary F., Goel, Anuj, Gorski, Mathia, Hayward, Caroline, Heard Costa, Nancy L., Jackson, Anne U., Jokinen, Eero, Kanoni, Stavroula, Kristiansson, Kati, Kutalik, Zoltán, Lahti, Jari, Luan, Jian'An, Mägi, Reedik, Mahajan, Anubha, Mangino, Massimo, Medina Gomez, Carolina, Monda, Keri L., Nolte, Ilja M., Pérusse, Loui, Prokopenko, Inga, Qi, Lu, Rose, Lynda M., Salvi, Erika, Smith, Megan T., Snieder, Harold, Standáková, Alena, Ju Sung, Yun, Tachmazidou, Ioanna, Teumer, Alexander, Thorleifsson, Gudmar, Van Der Harst, Pim, Walker, Ryan W., Wang, Sophie R., Wild, Sarah H., Willems, Sara M., Wong, Andrew, Zhang, Weihua, Albrecht, Eva, Couto Alves, Alexessander, Bakker, Stephan J. L., Barlassina, Cristina, Bartz, Traci M., Beilby, John, Bellis, Claire, Bergman, Richard N., Bergmann, Sven, Blangero, John, Blüher, Matthia, Boerwinkle, Eric, Bonnycastle, Lori L., Bornstein, Stefan R., Bruinenberg, Marcel, Campbell, Harry, Chen, Yii Der Ida, Chiang, Charleston W. K., Chines, Peter S., Collins, Francis S, Cucca, Fracensco, Cupples, L. Adrienne, D'Avila, Francesca, De Geus, Eco J. C., Dedoussis, George, Dimitriou, Maria, Döring, Angela, Eriksson, Johan G., Farmaki, Aliki Eleni, Farrall, Martin, Ferreira, Teresa, Fischer, Krista, Forouhi, Nita G., Friedrich, Nele, Gjesing, Anette Prior, Glorioso, Nicola, Graff, Mariaelisa, Grallert, Harald, Grarup, Niel, Gräßler, Jürgen, Grewal, Jagvir, Hamsten, Ander, Harder, Marie Neergaard, Hartman, Catharina A., Hassinen, Maija, Hastie, Nichola, Hattersley, Andrew Tym, Havulinna, Aki S., Heliövaara, Markku, Hillege, Han, Hofman, Albert, Holmen, Oddgeir, Homuth, Georg, Hottenga, Jouke Jan, Hui, Jennie, Husemoen, Lise Lotte, Hysi, Pirro G., Isaacs, Aaron, Ittermann, Till, Jalilzadeh, Shapour, James, Alan L., Jørgensen, Torben, Jousilahti, Pekka, Jula, Antti, Marie Justesen, Johanne, Justice, Anne E., Kähönen, Mika, Karaleftheri, Maria, Tee Khaw, Kay, Keinanen Kiukaanniemi, Sirkka M., Kinnunen, Leena, Knekt, Paul B., Koistinen, Heikki A., Kolcic, Ivana, Kooner, Ishminder K., Koskinen, Seppo, Kovacs, Peter, Kyriakou, Theodosio, Laitinen, Tomi, Langenberg, Claudia, Lewin, Alexandra M., Lichtner, Peter, Lindgren, Cecilia M., Lindström, Jaana, Linneberg, Allan, Lorbeer, Roberto, Lorentzon, Mattia, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Manunta, Paolo, Leach, Irene Mateo, Mcardle, Wendy L., Mcknight, Barbara, Mohlke, Karen L., Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Montasser, May E., Morris, Andrew P., Müller, Gabriele, Musk, Arthur W., Narisu, Narisu, Ong, Ken K., Oostra, Ben A., Osmond, Clive, Palotie, Aarno, Pankow, James S., Paternoster, Lavinia, Penninx, Brenda W., Pichler, Irene, Pilia, Maria G., Polašek, Ozren, Pramstaller, Peter P., Raitakari, Olli T, Rankinen, Tuomo, Rao, D. C., Rayner, Nigel W., Ribel Madsen, Rasmu, Rice, Treva K., Richards, Marcu, Ridker, Paul M., Rivadeneira, Fernando, Ryan, Kathy A., Sanna, Serena, Sarzynski, Mark A., Scholtens, Salome, Scott, Robert A., Sebert, Sylvain, Southam, Lorraine, Sparsø, Thomas Hempel, Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stolk, Ronald P., Strauch, Konstantin, Stringham, Heather M., Swertz, Morris A., Swift, Amy J., Tönjes, Anke, Tsafantakis, Emmanouil, Van Der Most, Peter J., Van Vliet Ostaptchouk, Jana V., Vandenput, Liesbeth, Vartiainen, Erkki, Venturini, Cristina, Verweij, Niek, Viikari, Jorma S., Vitart, Veronique, Vohl, Marie Claude, Vonk, Judith M., Waeber, Gérard, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Winkler, Thomas W., Wright, Alan F., Yerges Armstrong, Laura M., Zhao, Jing Hua, Carola Zillikens, M., Boomsma, Dorret I., Bouchard, Claude, Chambers, John C., Chasman, Daniel I., Cusi, Daniele, Gansevoort, Ron T., Gieger, Christian, Hansen, Torben, Hicks, Andrew A., Hu, Frank, Hveem, Kristian, Jarvelin, Marjo Riitta, Kajantie, Eero, Kooner, Jaspal S., Kuh, Diana, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lehtimäki, Terho, Metspalu, Andre, Njølstad, Inger, Ohlsson, Clae, Oldehinkel, Albertine J., Palmer, Lyle J., Pedersen, Oluf, Perola, Marku, Peters, Annette, Psaty, Bruce M., Puolijoki, Hannu, Rauramaa, Rainer, Rudan, Igor, Salomaa, Veikko, Schwarz, Peter E. H., Shudiner, Alan R., Smit, Jan H., Sørensen, Thorkild I. A., Spector, Timothy D., Stefansson, Kari, Stumvoll, Michael, Tremblay, Angelo, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, Völker, Uwe, Vollenweider, Peter, Wareham, Nicholas J., Watkins, Hugh, Wilson, James F., Zeggini, Eleftheria, Abecasis, Goncalo R., Boehnke, Michael, Borecki, Ingrid B., Deloukas, Pano, Van Duijn, Cornelia M., Fox, Caroline, Groop, Leif C., Heid, Iris M., Hunter, David J., Kaplan, Robert C., Mccarthy, Mark I., North, Kari E., O'Connell, Jeffrey R., Schlessinger, David, Thorsteinsdottir, Unnur, Strachan, David P., Frayling, Timothy, Hirschhorn, Joel N., Müller Nurasyid, Martina, Loos, Ruth J. F., Internal medicine, Psychiatry, EMGO - Mental health, Public Health, Epidemiology, Surgery, Internal Medicine, Erasmus MC other, and Child and Adolescent Psychiatry / Psychology
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Statistical methods, General Physics and Astronomy, Genome-wide association study, Genome-wide association studies, Mice, HEIGHT, Body Size, Mass index, 2. Zero hunger, Genetics, Principal Component Analysis, Multidisciplinary, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Anthropometry, Chemistry (all), Phenotype, Common, gene, body, shape, Multidisciplinary Sciences, Principal component analysis, Trait, Science & Technology - Other Topics, DIET-INDUCED OBESITY, Waist, Genotype, 515 Psychology, Science, EARLY-ONSET, Snp, BIOLOGY, HIP RATIO, Genome-wide association studies Statistical methods, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Physics and Astronomy (all), MASS INDEX, DISEASE ASSOCIATIONS, RESOURCE, MD Multidisciplinary, Humans, GENOME-WIDE ASSOCIATION, Biochemistry, Genetics and Molecular Biology (all), Science & Technology, Models, Genetic, ta1184, FAT DISTRIBUTION, General Chemistry, ta3121, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, 3111 Biomedicine, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Body mass index, Genome-Wide Association Study
Abstract: Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways., published version, peerReviewed
Published: 2016

245. The Genetic Overlap Between Hair and Eye Color

Author: Abdel Abdellaoui, Dorret I. Boomsma, Erik A. Ehli, Bochao D. Lin, Jouke J. Hottenga, Gareth E. Davies, Gonneke Willemsen, Meike Bartels, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Adult, Male, genetic structures, Population, Genome-wide association study, Population stratification, Genetic correlation, Polymorphism, Single Nucleotide, White People, Correlation, 03 medical and health sciences, Eye color, Humans, education, Genetics (clinical), Netherlands, Genetics, education.field_of_study, biology, integumentary system, Eye Color, Obstetrics and Gynecology, Middle Aged, biology.organism_classification, eye diseases, 030104 developmental biology, Genetics, Population, Phenotype, Pediatrics, Perinatology and Child Health, Female, sense organs, Cabello, Blond hair, Genome-Wide Association Study, Hair
Abstract: We identified the genetic variants for eye color by Genome-Wide Association Study (GWAS) in a Dutch Caucasian family-based population sample and examined the genetic correlation between hair and eye color using data from unrelated participants from the Netherlands Twin Register. With the Genome-wide Complex Trait Analysis software package, we found strong genetic correlations between various combinations of hair and eye colors. The strongest positive correlations were found for blue eyes with blond hair (0.87) and brown eyes with dark hair (0.71), whereas blue eyes with dark hair and brown eyes with blond hair showed the strongest negative correlations (-0.64 and -0.94, respectively). Red hair with green/hazel eyes showed the weakest correlation (-0.14). All analyses were corrected for age and sex, and we explored the effects of correcting for principal components (PCs) that represent ancestry and describe the genetic stratification of the Netherlands. When including the first three PCs as covariates, the genetic correlations between the phenotypes disappeared. This is not unexpected since hair and eye colors strongly indicate the ancestry of an individual. This makes it difficult to separate the effects of population stratification and the true genetic effects of variants on these particular phenotypes.
Published: 2016

246. Author response: Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Author: Ingunn Brandt, Glen E. Duncan, Juan F. Sánchez-Romera, Corrado Fagnani, Adam Domonkos Tarnoki, Alice M. Gregory, Shandell Pahlen, Yoshie Yokoyama, Hermine H. Maes, Qihua Tan, Hoe-Uk Jeong, Robert Vlietinck, Dongfeng Zhang, Matt McGue, Robert F. Krueger, Anna K. Dahl-Aslan, David A. Butler, Brooke M. Huibregtse, Kelly L. Klump, Nancy L. Pedersen, Paul Lichtenstein, Massimo Mangino, Gonneke Willemsen, Tracy L. Nelson, Robin P. Corley, Kayoung Lee, S. Alexandra Burt, Sari Aaltonen, Michael J. Lyons, Karri Silventoinen, Sarah E. Medland, Christian Kandler, Lucía Colodro-Conde, Ruth Krasnow, Yoshinori Iwatani, Gary E. Swan, Lindon J. Eaves, Tessa L. Cutler, Jennifer R. Harris, Juan R. Ordoñana, Laura A. Baker, Chika Honda, Catherine Derom, Carol E. Franz, Thorkild I. A. Sørensen, Margaret Gatz, Gombojav Bayasgalan, Nicholas G. Martin, David Laszlo Tarnoki, Toos C. E. M. van Beijsterveldt, William S. Kremen, Tom A. McAdams, Catherine Tuvblad, Tim D. Spector, Cristina D'Ippolito, Kaare Christensen, Danshiitsoodol Narandalai, Esther Rebato, Kauko Heikkilä, Judy L. Silberg, Mikio Watanabe, Dorret I. Boomsma, Jaakko Kaprio, Patrik K. E. Magnusson, Axel Skytthe, Jacob v. B. Hjelmborg, Genevieve Lachance, Fruhling Rijsdijk, Keith E. Whitfield, Reijo Sund, Fazil Aliev, Grant W. Montgomery, Aline Jelenkovic, Amie E. Hwang, Kerry L. Jang, Thalia C. Eley, Yun-Mi Song, Finn Rasmussen, Kirsten Ohm Kyvik, Sisira Siribaddana, Per Tynelius, Athula Sumathipala, Yoon-Mi Hur, Zengchang Pang, Sevgi Y. Öncel, Joohon Sung, John L. Hopper, Thomas M. Mack, Ruth J. F. Loos, Jack Goldberg, Fujio Inui, Andreas Busjahn, Meike Bartels, Maria Antonietta Stazi, Wendy Cozen, Matthew Hotopf, Sarah Yang, Dedra Buchwald, and Thomas Sevenius Nilsen
Subjects: 03 medical and health sciences, 0302 clinical medicine, 05 social sciences, 0501 psychology and cognitive sciences, 050102 behavioral science & comparative psychology, Human height, Biology, Birth cohort, 030217 neurology & neurosurgery, Demography
Published: 2016

247. Genetic variants linked to education predict longevity

Author: Chris Power, Gail Davies, Ilaria Gandin, Panagiotis Deloukas, Jennifer E. Huffman, Pascal Timshel, Albert V. Smith, A. Kong, Paul Lichtenstein, Joseph K. Pickrell, Philipp Koellinger, P. L. De Jager, Reedik Mägi, G. B. Chen, Neil Pendleton, B. V. Halldórsson, George Dedoussis, Antti-Pekka Sarin, Natalia Pervjakova, Veikko Salomaa, Simona Vaccargiu, Ozren Polasek, K. H. Jöckel, Elisabeth Steinhagen-Thiessen, Y. Milaneschi, Jessica D. Faul, Patricia A. Boyle, Patrik K. E. Magnusson, Igor Rudan, Christopher P. Nelson, Vilmundur Gudnason, John Attia, Jürgen Wellmann, Kristi Läll, Konstantin Strauch, Stuart J. Ritchie, Markus Perola, Nicola Pirastu, Klaus Bønnelykke, Robert Karlsson, R. de Vlaming, Liisa Keltigangas-Jarvinen, Thomas Meitinger, Riccardo E. Marioni, Anu Loukola, Barbera Franke, Reinhold Schmidt, Maël Lebreton, Sven Oskarsson, E. Mihailov, Harm-Jan Westra, David R. Weir, Aldi T. Kraja, Niek Verweij, Peter M. Visscher, Hans-Jörgen Grabe, Johannes H. Brandsma, Mark Adams, R. J. Scott, G. Thorleifsson, Tõnu Esko, Mika Kähönen, Saskia P. Hagenaars, Patrick Turley, Johannes Waage, Peter Lichtner, Dragana Vuckovic, Antonietta Robino, Henry Völzke, Lydia Quaye, C. de Leeuw, Marika Kaakinen, Wei Zhao, Abdel Abdellaoui, Reka Nagy, Pedro Marques-Vidal, Johan G. Eriksson, Alan F. Wright, Andres Metspalu, Lavinia Paternoster, Momoko Horikoshi, Jan A. Staessen, Tarunveer S. Ahluwalia, Tian Liu, Martin Kroh, Aldo Rustichini, Giorgia Girotto, Cristina Venturini, Lili Milani, Jennifer A. Smith, Ginevra Biino, Tessel E. Galesloot, Michael A. Horan, Gerardus A. Meddens, James F. Wilson, Francesco Cucca, Peter Vollenweider, Erika Salvi, P. J. van der Most, Jari Lahti, Campbell A, David Laibson, Andrew Bakshi, Wolfgang Hoffmann, Tomi Mäki-Opas, Andreas J. Forstner, C M van Duijn, Nicholas G. Martin, Jonathan Marten, Ute Bültmann, Olli T. Raitakari, David A. Bennett, A.G. Uitterlinden, J. E. De Neve, Ingrid B. Borecki, WD Hill, Bo Jacobsson, Antti Latvala, Katri Räikkönen, Michael B. Miller, Jonathan P. Beauchamp, S. J. van der Lee, Ilja Demuth, Stavroula Kanoni, Veronique Vitart, Elina Hyppönen, N. Eklund, Francesco P. Cappuccio, Robert F. Krueger, Maria Pina Concas, Jaime Derringer, F. J.A. Van Rooij, Helena Schmidt, Patrick J. F. Groenen, Valur Emilsson, Rico Rueedi, Aysu Okbay, Georg Homuth, Edith Hofer, W. E. R. Ollier, Hannah Campbell, Paolo Gasparini, Mark Alan Fontana, Magnus Johannesson, Seppo Koskinen, Christopher F. Chabris, Jouke-Jan Hottenga, Christine Meisinger, Kari Stefansson, Jun Ding, Tia Sorensen, Brenda W.J.H. Penninx, Michelle N. Meyer, James J. Lee, Diego Vozzi, Gonneke Willemsen, K. Petrovic, Sarah E. Medland, Mary F. Feitosa, Henning Tiemeier, L. J. Launer, William G. Iacono, Massimo Mangino, Tune H. Pers, S. E. Baumeister, Christopher Oldmeadow, Grant W. Montgomery, Marjo-Riitta Järvelin, Jaakko Kaprio, Catharine R. Gale, S.F.W. Meddens, Kevin Thom, Klaus Berger, Pablo V. Gejman, Lude Franke, Gyda Bjornsdottir, Daniel J. Benjamin, Steven F. Lehrer, Krista Fischer, Alan R. Sanders, S. Ulivi, Katharina E. Schraut, Tim D. Spector, Amy Hofman, Matt McGue, Terho Lehtimäki, D. C. Liewald, Hans Bisgaard, L. Eisele, Astanand Jugessur, George Davey Smith, T.B. Harris, A.R. Thurik, Cornelius A. Rietveld, David Schlessinger, Z. Kutalik, David J. Porteous, Lynne J. Hocking, N J Timpson, A. Palotie, Lambertus A. Kiemeney, Ian J. Deary, Sharon L.R. Kardia, Peter K. Joshi, Nilesh J. Samani, Michael A. Province, Börge Schmidt, Richa Gupta, Carmen Amador, Erin B. Ware, Joyce Y. Tung, Ioanna-Panagiota Kalafati, Lars Bertram, Caroline Hayward, P. van der Harst, Penelope A. Lind, Kadri Kaasik, N.A. Furlotte, Sarah E. Harris, B. St Pourcain, Susan M. Ring, Zhihong Zhu, Alexander Teumer, Behrooz Z. Alizadeh, Judith M. Vonk, Blair H. Smith, A Payton, Wouter J. Peyrot, Jacob Gratten, Douglas F. Levinson, C Gieger, Leanne M. Hall, Andrew Heath, Mario Pirastu, Peter Eibich, Nancy L. Pedersen, Ronny Myhre, Antonio Terracciano, David M. Evans, Raymond A. Poot, Uwe Völker, Dorret I. Boomsma, Clemens Baumbach, Unnur Thorsteinsdottir, Ivana Kolcic, Jia-Shu Yang, Dalton Conley, A. A. Vinkhuyzen, Danielle Posthuma, Karl-Oskar Lindgren, Olga Rostapshova, Jonas Bacelis, Daniele Cusi, Yong Qian, Bjarni Gunnarsson, George McMahon, Elizabeth G. Holliday, Pamela A. F. Madden, David A. Hinds, David Cesarini, Jianxin Shi, Najaf Amin, Dale R. Nyholt, Applied Economics, Epidemiology, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Aletta Jacobs School of Public Health, Public Health Research (PHR), Stem Cell Aging Leukemia and Lymphoma (SALL), Cardiovascular Centre (CVC), Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, EMGO - Mental health, Complex Trait Genetics, Biological Psychology, Marioni, RE, Ritchie, SJ, Joshi, PK, Hagenaars, SP, Hypponen, E, Benjamin, DJ, Social Science Genetic Association Consortium, Marioni, Re, Ritchie, Sj, Joshi, Pk, Hagenaars, Sp, Okbay, A, Fischer, K, Adams, Mj, Hill, Wd, Davies, G, Nagy, R, Amador, C, Läll, K, Metspalu, A, Liewald, Dc, Campbell, A, Wilson, Jf, Hayward, C, Esko, T, Porteous, Dj, Gale, Cr, Deary, Ij, Beauchamp, Jp, Fontana, Ma, Lee, Jj, Pers, Th, Rietveld, Ca, Turley, P, Chen, Gb, Emilsson, V, Meddens, Sf, Oskarsson, S, Pickrell, Jk, Thom, K, Timshel, P, de Vlaming, R, Abdellaoui, A, Ahluwalia, T, Bacelis, J, Baumbach, C, Bjornsdottir, G, Brandsma, Jh, Concas, MARIA PINA, Derringer, J, Furlotte, Na, Galesloot, Te, Girotto, Giorgia, Gupta, R, Hall, Lm, Harris, Se, Hofer, E, Horikoshi, M, Huffman, Je, Kaasik, K, Kalafati, Ip, Karlsson, R, Kong, A, Lahti, J, van der Lee, Sj, de Leeuw, C, Lind, Pa, Lindgren, Ko, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, Mb, van der Most, Pj, Oldmeadow, C, Payton, A, Pervjakova, N, Peyrot, Wj, Qian, Y, Raitakari, O, Rueedi, R, Salvi, E, Schmidt, B, Schraut, Ke, Shi, J, Smith, Av, Poot, Ra, St Pourcain, B, Teumer, A, Thorleifsson, G, Verweij, N, Vuckovic, Dragana, Wellmann, J, Westra, Hj, Yang, J, Zhao, W, Zhu, Z, Alizadeh, Bz, Amin, N, Bakshi, A, Baumeister, Se, Biino, G, Bønnelykke, K, Boyle, Pa, Campbell, H, Cappuccio, Fp, De Neve, Je, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, Dm, Faul, Jd, Feitosa, Mf, Forstner, Aj, Gandin, Ilaria, Gunnarsson, B, Halldórsson, Bv, Harris, Tb, Heath, Ac, Hocking, Lj, Holliday, Eg, Homuth, G, Horan, Ma, Hottenga, Jj, de Jager, Pl, Jugessur, A, Kaakinen, Ma, Kähönen, M, Kanoni, S, Keltigangas Järvinen, L, Kiemeney, La, Kolcic, I, Koskinen, S, Kraja, At, Kroh, M, Kutalik, Z, Latvala, A, Launer, Lj, Lebreton, Mp, Levinson, Df, Lichtenstein, P, Lichtner, P, Loukola, A, Madden, Pa, Mägi, R, Mäki Opas, T, Marques Vidal, P, Meddens, Ga, Mcmahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, Gw, Myhre, R, Nelson, Cp, Nyholt, Dr, Ollier, We, Palotie, A, Paternoster, L, Pedersen, Nl, Petrovic, Ke, Räikkönen, K, Ring, Sm, Robino, Antonietta, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, Ar, Sarin, Ap, Schmidt, H, Scott, Rj, Smith, Bh, Smith, Ja, Staessen, Ja, Steinhagen Thiessen, E, Strauch, K, Terracciano, A, Tobin, Md, Ulivi, Sheila, Vaccargiu, S, Quaye, L, van Rooij, Fj, Venturini, C, Vinkhuyzen, Aa, Völker, U, Völzke, H, Vonk, Jm, Vozzi, Diego, Waage, J, Ware, Eb, Willemsen, G, Attia, Jr, Bennett, Da, Berger, K, Bertram, L, Bisgaard, H, Boomsma, Di, Borecki, Ib, Bultmann, U, Chabris, Cf, Cucca, F, Cusi, D, Dedoussis, Gv, van Duijn, Cm, Eriksson, Jg, Franke, B, Franke, L, Gasparini, Paolo, Gejman, Pv, Gieger, C, Grabe, Hj, Gratten, J, Groenen, Pj, Gudnason, V, van der Harst, P, Hinds, Da, Hoffmann, W, Iacono, Wg, Jacobsson, B, Järvelin, Mr, Jöckel, Kh, Kaprio, J, Kardia, Sl, Lehtimäki, T, Lehrer, Sf, Magnusson, Pk, Martin, Ng, Mcgue, M, Pendleton, N, Penninx, Bw, Perola, M, Pirastu, Nicola, Pirastu, M, Polasek, O, Posthuma, D, Power, C, Province, Ma, Samani, Nj, Schlessinger, D, Schmidt, R, Sørensen, Ti, Spector, Td, Stefansson, K, Thorsteinsdottir, U, Thurik, Ar, Timpson, Nj, Tiemeier, H, Tung, Jy, Uitterlinden, Ag, Vitart, V, Vollenweider, P, Weir, Dr, Wright, Af, Conley, Dc, Krueger, Rf, Smith, Gd, Hofman, A, Laibson, Di, Medland, Se, Meyer, Mn, Johannesson, M, Visscher, Pm, Koellinger, Pd, Cesarini, D, and Benjamin, Dj
Subjects: Netherlands Twin Register (NTR), 0301 basic medicine, Male, Parents, education: longevity: prediction: polygenic score [genetics], Multifactorial Inheritance, polygenic, Lebenserwartung, Cohort Studies, 0302 clinical medicine, Databases, Genetic, Medicine, genetics, polygenic score, longevity, education, gene, Soziales und Gesundheit, media_common, Aged, 80 and over, education, Multidisciplinary, Longevity, Middle Aged, Biobank, humanities, 3. Good health, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, Educational Status, Female, Cohort study, Estonia, education, longevity, polygenic, Offspring, media_common.quotation_subject, Kultursektor, Prognose, Lernen, Lower risk, Education, 03 medical and health sciences, longevity, SDG 3 - Good Health and Well-being, Commentaries, Polygenic score, Journal Article, Genetics, Humans, Non-Profit-Sektor, Genetic Association Studies, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, ta1184, Genetic Variation, prediction, Educational attainment, United Kingdom, Gesundheitsstatistik, 030104 developmental biology, Genetic epidemiology, Scotland, Gesundheitszustand, Genetische Forschung, business, Prediction, Bildung, 030217 neurology & neurosurgery, Demography
Abstract: Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total n deaths = 79,702) and ∼2.4% lower risk for fathers (total n deaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity. Marioni RE, Ritchie SJ, Joshi PK, Hagenaars SP, Okbay A, Fischer K, Adams MJ, Hill WD, Davies G, Social Science Genetic Association Consortium, Nagy R, Amador C, Läll K, Metspalu A, Liewald DC, Campbell A, Wilson JF, Hayward C, Esko T, Porteous DJ, Proceedings of the National Academy of Sciences of the United States of America, 2016, vol. 113, no. 47, pp. 13366-13371, 2016 Refereed/Peer-reviewed
Published: 2016

248. Genome-wide associations for birth weight and correlations with adult disease

Author: Anubha Mahajan, George McMahon, Charlotta Pisinger, Timothy M. Frayling, Elisabeth M. van Leeuwen, Felix R. Day, Virpi Lindi, Allan Vaag, Debbie A Lawlor, Natalie R. van Zuydam, Peter Kovacs, David Torrents, Bjarke Feenstra, Peter Vollenweider, David P. Strachan, Krina T. Zondervan, John R. B. Perry, Jorma Viikari, Pedro Marques-Vidal, Kalliope Panoutsopoulou, Ruifang Li-Gao, Juan Fernández-Tajes, Carolina Medina-Gomez, Nicole M. Warrington, Josep M. Mercader, Antje Körner, David M. Evans, Albert Hofman, Hans Bisgaard, Amanda J. Bennett, Eleanor Davies, Linda S. Adair, Oluf Pedersen, Mustafa Atalay, Sylvain Sebert, Ying Wu, Haja N. Kadarmideen, Ronald C.W. Ma, Lawrence J. Beilin, David M. Hougaard, Diana L. Cousminer, Louise A. Diver, Jing Hua Zhao, Nilufer Rahmioglu, Peter K. Joshi, Neil R. Robertson, Johannes Waage, Hugoline G. de Haan, Jens-Christian Holm, Dale R. Nyholt, Torben Hansen, Sara M. Willems, Sílvia Bonàs-Guarch, Carol A. Wang, Rico Rueedi, Lavinia Paternoster, James F. Wilson, Cilius Esmann Fonvig, Leo-Pekka Lyytikäinen, Hanieh Yaghootkar, Momoko Horikoshi, Gonneke Willemsen, Dennis O. Mook-Kanamori, Lisbeth Carstensen, Mariona Bustamante, Emil V. R. Appel, Christian Theil Have, Rebecca M. Reynolds, Niels Grarup, Seang-Mei Saw, Yik Ying Teo, Brian R. Walker, Anke Tönjes, Christopher J. Groves, Andrew P. Morris, Katja Pahkala, Marjolein N. Kooijman, Kyle J. Gaulton, Eskil Kreiner, Michael Stumvoll, Eleftheria Zeggini, Vincent W. V. Jaddoe, Zoltán Kutalik, Scott M. MacKenzie, George Davey Smith, Christine Power, Denise M. Scholtens, Joachim Heinrich, Samuel E. Jones, William L. Lowe, Eco J. C. de Geus, Jonathan P. Bradfield, Andrew T. Hattersley, Janine F. Felix, Wing Hung Tam, Frits R. Rosendaal, Wieland Kiess, Claudia H. T. Tam, Inga Prokopenko, Terho Lehtimäki, Frank D. Mentch, Marjo-Riitta Järvelin, Struan F.A. Grant, Santhi K. Ganesh, Fernando Rivadeneira, Thorkild I. A. Sørensen, André G. Uitterlinden, Marie Standl, Jian'an Luan, Gibran Hemani, Marcus A. Tuke, Andrew R. Wood, Robert A. Scott, Cæcilie Trier, Tarunveer S. Ahluwalia, Michael Nodzenski, Jouke-Jan Hottenga, Ken K. Ong, Po-Ru Loh, Nicholas J. Timpson, George Dedoussis, Friman Sánchez, Mark I. McCarthy, Frank Geller, Harri Niinikoski, Martine Vrijheid, Hakon Hakonarson, John P. Newnham, Xu Wang, Elina Hyppönen, Johan G. Eriksson, Craig E. Pennell, Niina Pitkänen, Rachel M. Freathy, Elisabeth Widen, Judith B. Borja, Karen L. Mohlke, Mads Melbye, Carla M. T. Tiesler, Susan M. Ring, Jessica Tyrrell, Elisabeth Thiering, Timo A. Lakka, Eileen Tai-Hui Boh, Olli T. Raitakari, Nicholas J. Wareham, Mario Murcia, Natalia Vilor-Tejedor, Katherine S. Ruth, Dorret I. Boomsma, Harry Campbell, Vasiliki Lagou, Robin N Beaumont, Klaus Bønnelykke, Claudia Langenberg, Catharina E. M. van Beijsterveldt, Mika Kähönen, Mads V. Hollegaard, Frank J.A. van Rooij, Katharina E. Schraut, Ioanna Ntalla, Raimo Joro, Cornelia M. van Duijn, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Day, Felix [0000-0003-3789-7651], Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Zhao, Jing Hua [0000-0003-4930-3582], Wareham, Nicholas [0000-0003-1422-2993], Ong, Kenneth [0000-0003-4689-7530], Perry, John [0000-0001-6483-3771], Apollo - University of Cambridge Repository, Erasmus MC other, Medical Microbiology & Infectious Diseases, Epidemiology, Medical Oncology, Child and Adolescent Psychiatry / Psychology, Public Health, Internal Medicine, Pediatrics, Horikoshi, Momoko, Beaumont, Robin N, Day, Felix R, Warrington, Nicole, Hyppönen, Elina, and Freathy, Rachel M
Subjects: Male, 0301 basic medicine, Netherlands Twin Register (NTR), Aging, Datasets as Topic, Physiology, Blood Pressure, Genome-wide association study, Coronary Artery Disease, Type 2 diabetes, Bioinformatics, CHARGE Consortium Hematology Working Group, Cohort Studies, 0302 clinical medicine, Birth Weight, Insulin, Glucose homeostasis, 030212 general & internal medicine, education.field_of_study, Multidisciplinary, Anthropometry, 3. Good health, Phenotype, Female, Glycogen, Signal Transduction, Adult, hypertension, Genotype, General Science & Technology, Birth weight, intrauterine growth, Population, Quantitative trait locus, Biology, Article, quantitative trait, Genomic Imprinting, 03 medical and health sciences, Fetus, SDG 3 - Good Health and Well-being, Early Growth Genetics (EGG) Consortium, MD Multidisciplinary, Genetic variation, medicine, Humans, metabolic disorders, Genetic Predisposition to Disease, education, genome, Genetic association, Genetic Variation, birth weight, ta3121, Chromatin Assembly and Disassembly, medicine.disease, ta3123, Glucose, 030104 developmental biology, Diabetes Mellitus, Type 2, Genetic Loci, genome-wide association studies, adult disease, Genome-Wide Association Study
Abstract: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P&thinsp
Published: 2016

249. Genetic variants in RBFOX3 are associated with sleep latency

Author: Igor Rudan, Tõnu Esko, Wilfred F. J. van IJcken, Alan F. Wright, Caroline Hayward, Nathaniel F. Watson, Ben A. Oostra, Karla V. Allebrandt, Scott A. Melville, Steven R. Cummings, Aaron Isaacs, Gonneke Willemsen, Yurii S. Aulchenko, Albert Hofman, Fran Borovečki, Maris Teder-Laving, Sina A. Gharib, Brenda W.J.H. Penninx, Cornelia M. van Duijn, Josine G. van Mill, Dorret I. Boomsma, Harry Campbell, James F. Wilson, Katie L. Stone, Rutger W W Brouwer, Philip R. Gehrman, Annemarie I. Luik, Ozren Polasek, Naresh M. Punjabi, Jouke-Jan Hottenga, Jennifer E. Huffman, Daniel S. Evans, Martina Müller-Nurasyid, Ashley van der Spek, Andrew A. Hicks, Susan Redline, Peter P. Pramstaller, Fabiola M. Del Greco, Rudolf S N Fehrmann, Bertram Müller-Myhsok, Nicole Vogelzangs, Man Li, Lude Franke, Edwin Oole, Ayse Demirkan, Lina Zgaga, Karin Hek, Mirjam C G N van den Hout, Wen Hong Linda Kao, Gregory J. Tranah, Enda M. Byrne, Bruce M. Psaty, Hamdi Mbarek, Martha Merrow, Kristin D. Marciante, Josef Coresh, Henning Tiemeier, Grant W. Montgomery, Till Roenneberg, Susan Campbell, Ivana Kolcic, Juha Karjalainen, Zoran Dogas, Andres Metspalu, Ting Hsu Chen, Najaf Amin, André G. Uitterlinden, Nicholas G. Martin, Daniel J. Gottlieb, Andrew C. Heath, Thomas Meitinger, Heinz Erich Wichmann, Jacqueline M. Vink, Evelin Mihailov, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Biochemie, RS: FHML MaCSBio, RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, Psychiatry, EMGO - Mental health, Epidemiology, Cell biology, Internal Medicine, Clinical Genetics, Child and Adolescent Psychiatry / Psychology, and Biological Psychology
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), EXPRESSION, Candidate gene, medicine.medical_specialty, Single-nucleotide polymorphism, Genome-wide association study, Delayed sleep phase, Nerve Tissue Proteins, DETERMINANTS, Biology, RECORDED SLEEP, Polymorphism, Single Nucleotide, Synaptic Transmission, Article, ONSET INSOMNIA, SELF-REPORT, sleep latency, gene, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Genetic linkage, Molecular genetics, Genetics, medicine, Insomnia, IMPUTATION, Humans, GENOME-WIDE ASSOCIATION, Genetics (clinical), Genetic association, LINKAGE ANALYSIS, Brain, Antigens, Nuclear, medicine.disease, FAMILY, 030104 developmental biology, CANDIDATE-GENE, medicine.symptom, Sleep, Developmental Psychopathology, 030217 neurology & neurosurgery
Abstract: Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values
Published: 2016

250. Genomic analyses for age at menarche identify 389 independent signals and indicate BMI-independent effects of puberty timing on cancer susceptibility

Author: Nora Franceschini, Rico Rueedi, Gerardo Heiss, Behrooz Z. Alizadeh, Marike Gabrielson, Henry Völzke, Daniela Ruggiero, Judith S. Brand, Stig E. Bojesen, Iffat Rahman, Fergus J. Couch, Patrick Sulem, Harold Snieder, Jenny Chang-Claude, Caterina Barbieri, Ute Hamann, Hinds D, Pascal Guénel, Amanda B. Spurdle, Paul M. Ridker, Ulla Sovio, Roger L. Milne, Hamdi Mbarek, H Brenner, Hilary K. Finucane, Maristella Steri, Lude Franke, Emmi Tikkanen, Ivana Kolcic, Vitart, Ken K. Ong, Alison M. Dunning, Aarno Palotie, Caroline Hayward, Jouke J. Hottenga, Abhishek Sarkar, Stefania Lenarduzzi, Nicholas G. Martin, Katharina E. Schraut, Eva Albrecht, Hiltrud Brauch, Lisette Stolk, Joop S.E. Laven, Penelope A. Lind, Ilaria Gandin, Patrik K. E. Magnusson, Ellen A. Nohr, Tanguy Corre, Jing Hua Zhao, N J Timpson, Jenny A. Visser, Harald Grallert, P. A. Fasching, Susan M. Ring, Stöckl D, Grant W. Montgomery, Marzyeh Amini, Velez Edwards Dr, Thomas Meitinger, Qinghua Wang, David Karasik, Daniel I. Chasman, Nicholas J. Wareham, Alexander Teumer, Mellissa C. Southey, Kathryn L. Lunetta, S. E. Medland, Dieter Flesch-Janys, Maartje J. Hooning, Lili Milani, D Lambrechts, Ozren Polasek, Po-Ru Loh, James F. Wilson, Campbell A, Julian Peto, Ellen W. Demerath, Christian Gieger, de Geus Ej, Cox A, Javier Benítez, Mitul Shah, Eric Boerwinkle, Matthias W. Beckmann, Thorsteindottir U, Julie E. Buring, De Vivo I, Hannes Helgason, Paolo Radice, Tracy A. O'Mara, L. J. Launer, D. F. Gudbjartsson, Frits R. Rosendaal, C.A. Hartman, Stefania Bandinelli, Felix R. Day, Lynda M. Rose, van Dijk Kw, Natalia Perjakova, Anneli Pouta, Igor Rudan, Sven Bergmann, Kamila Czene, Georgia Chenevix-Trench, Pau Navarro, Sean Whalen, Heli Nevanlinna, Teresa Nutile, Diana L. Cousminer, Albert V. Smith, Massimo Mangino, Uwe Völker, Michela Traglia, Lindsay Fernández-Rhodes, Ayush Giri, Linda Broer, Albertine J. Oldehinkel, Isabel dos-Santos-Silva, Peter Vollenweider, Jian'an Luan, Nancy L. Pedersen, Irene L. Andrulis, Reedik Mägi, Robert Winqvist, Gonneke Willemsen, John L. Hopper, Gudnason, Marjanka K. Schmidt, David G. Hunter, Robert A. Scott, T.B. Harris, Joanne M. Murabito, David J. Porteous, Harry Campbell, Eleonora Porcu, D.I. Boomsma, Thibaud Boutin, M. A. Ikram, Doug Easton, Magdalena Zoledziewska, Meir J. Stampfer, Katherine S. Pollard, Eulalia Catamo, Tõnu Esko, M-R Jarvelin, Laura Crisponi, Claudia Langenberg, Marek Zygmunt, Antonietta Robino, Emily Hallberg, Manjeet K. Bolla, Ruth Ks, Bruce H W Wolffenbuttel, Lavinia Paternoster, Tyrer Jp, P. Kraft, George Davey-Smith, Robert Karlsson, Graham G. Giles, Jingmei Li, Pharoah Pd, Segrè Av, Marina Ciullo, Perry, Brumat Marco, Peter K. Joshi, Chunyan He, Sara Lindström, Joe Dennis, Thérèse Truong, Yongmei Liu, Anna Marie Mulligan, Mike A. Nalls, Cinzia Sala, K. Stefansson, Murray A, Debbie A Lawlor, Tung Jy, Deborah J. Thompson, Dennis O. Mook-Kanamori, Daniela Toniolo, Luigi Ferrucci, Peter Devilee, S. Chanock, Cristina Menni, George McMahon, Murielle Bochud, A. Metspalu, Tomohiro Tanaka, E. Widen, Hae Kyung Im, Dale R. Nyholt, Ilja M. Nolte, Thomas Brüning, Christina Meisinger, Annette Peters, Kyriaki Michailidou, Per Hall, Rossella Sorice, Genevieve Lachance, Johan G. Eriksson, Francesco Cucca, A.G. Uitterlinden, Z. Kutalik, Mark I. McCarthy, Frank B. Hu, Konstantin Strauch, Tim D. Spector, Elisabeth Altmaier, S. Ulivi, Alkes L. Price, Arto Mannermaa, Raymond Noordam, and de Mutsert R
Subjects: Genetics, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Genotype, Menarche, Trait, Cancer susceptibility, Genomics, Biology, 030304 developmental biology
Abstract: The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Here, we analyse 1000-Genome reference panel imputed genotype data on up to ~370,000 women and identify 389 independent signals (all P−8) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4% of the population variance in age at menarche, corresponding to one quarter of the estimated heritability. We implicate over 250 genes via coding variation or associated gene expression, and demonstrate enrichment across genes active in neural tissues. We identify multiple rare variants near the imprinted genes MKRN3 and DLK1 that exhibit large effects on menarche only when paternally inherited. Disproportionate effects of variants on early or late puberty timing are observed: single variant and heritability estimates are larger for early than late puberty timing in females. The opposite pattern is seen in males, with larger estimates for late than early puberty timing. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support new causal links with adult cancer risks.
Published: 2016
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