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1. Genetic architecture of heart failure with preserved versus reduced ejection fraction

Author

Jacob, Joseph, Chang, Liu, Qin, Hui, Krishna, Aragam, Zeyuan, Wang, Brian, Charest, Jennifer E, Huffman, Jacob M, Keaton, Todd L, Edwards, Serkalem, Demissie, Luc, Djousse, Juan P, Casas, J Michael, Gaziano, Kelly, Cho, Peter W F, Wilson, Lawrence S, Phillips, and Christopher J, O'Donnell

Abstract

Pharmacologic clinical trials for heart failure with preserved ejection fraction have been largely unsuccessful as compared to those for heart failure with reduced ejection fraction. Whether differences in the genetic underpinnings of these major heart failure subtypes may provide insights into the disparate outcomes of clinical trials remains unknown. We utilize a large, uniformly phenotyped, single cohort of heart failure sub-classified into heart failure with reduced and with preserved ejection fractions based on current clinical definitions, to conduct detailed genetic analyses of the two heart failure sub-types. We find different genetic architectures and distinct genetic association profiles between heart failure with reduced and with preserved ejection fraction suggesting differences in underlying pathobiology. The modest genetic discovery for heart failure with preserved ejection fraction (one locus) compared to heart failure with reduced ejection fraction (13 loci) despite comparable sample sizes indicates that clinically defined heart failure with preserved ejection fraction likely represents the amalgamation of several, distinct pathobiological entities. Development of consensus sub-phenotyping of heart failure with preserved ejection fraction is paramount to better dissect the underlying genetic signals and contributors to this highly prevalent condition.

Published
2022

2. 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
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3. Corrigendum: Rare coding variants and X-linked loci associated with age at menarche

Author

Kathryn L. Lunetta, Felix R. Day, Patrick Sulem, Katherine S. Ruth, Joyce Y. Tung, David A. Hinds, Tõnu Esko, Cathy E. Elks, Elisabeth Altmaier, Chunyan He, Jennifer E. Huffman, Evelin Mihailov, Eleonora Porcu, Antonietta Robino, Lynda M. Rose, Ursula M. Schick, Lisette Stolk, Alexander Teumer, Deborah J. Thompson, Michela Traglia, Carol A. Wang, Laura M. Yerges-Armstrong, and Antonis C. Antoniou

Published
2015
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4. Rare coding variants and X-linked loci associated with age at menarche

Author

Kathryn L. Lunetta, Felix R. Day, Patrick Sulem, Katherine S. Ruth, Joyce Y. Tung, David A. Hinds, Tõnu Esko, Cathy E. Elks, Elisabeth Altmaier, Chunyan He, Jennifer E. Huffman, Evelin Mihailov, Eleonora Porcu, Antonietta Robino, Lynda M. Rose, Ursula M. Schick, Lisette Stolk, Alexander Teumer, Deborah J. Thompson, Michela Traglia, Carol A. Wang, Laura M. Yerges-Armstrong, Antonis C. Antoniou, Caterina Barbieri, Andrea D. Coviello, Francesco Cucca, Ellen W. Demerath, Alison M. Dunning, Ilaria Gandin, Megan L. Grove, Daniel F. Gudbjartsson, Lynne J. Hocking, Albert Hofman, Jinyan Huang, Rebecca D. Jackson, David Karasik, Jennifer Kriebel, Ethan M. Lange, Leslie A. Lange, Claudia Langenberg, Xin Li, Jian'an Luan, Reedik Mägi, Alanna C. Morrison, Sandosh Padmanabhan, Ailith Pirie, Ozren Polasek, David Porteous, Alex P. Reiner, Fernando Rivadeneira, Igor Rudan, Cinzia F. Sala, David Schlessinger, Robert A. Scott, Doris Stöckl, Jenny A. Visser, Uwe Völker, Diego Vozzi, James G. Wilson, Marek Zygmunt, Nita G. Forouhi, Nicola D. Kerrison, Stephen J. Sharp, Matt Sims, Inês Barroso, Panos Deloukas, Mark I. McCarthy, Larraitz Arriola, Beverley Balkau, Aurelio Barricarte, Heiner Boeing, Paul W. Franks, Carlos Gonzalez, Sara Grioni, Rudolf Kaaks, Timothy J. Key, Carmen Navarro, Peter M. Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María‐José Sánchez, Nadia Slimani, Anne Tjonneland, Rosario Tumino, Daphne L. van der A, Yvonne T. van der Schouw, Elio Riboli, Blair H. Smith, Archie Campbell, Ian J. Deary, Andrew M. McIntosh, Eric Boerwinkle, Julie E. Buring, Laura Crisponi, Douglas F. Easton, Caroline Hayward, Frank B. Hu, Simin Liu, Andres Metspalu, Craig E. Pennell, Paul M. Ridker, Konstantin Strauch, Elizabeth A. Streeten, Daniela Toniolo, André G. Uitterlinden, Sheila Ulivi, Henry Völzke, Nicholas J. Wareham, Melissa Wellons, Nora Franceschini, Daniel I. Chasman, Unnur Thorsteinsdottir, Anna Murray, Kari Stefansson, Joanne M. Murabito, Ken K. Ong, John R. B. Perry

Published
2015
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5. Correction: Corrigendum: Rare coding variants and X-linked loci associated with age at menarche

Author

Elizabeth A. Streeten, Joanne M. Murabito, Alison M. Dunning, Igor Rudan, Tõnu Esko, Lynne J. Hocking, Ailith Pirie, Douglas F. Easton, Laura Crisponi, Antonietta Robino, Ken K. Ong, David Karasik, Paul M. Ridker, Leslie A. Lange, Eleonora Porcu, Kathryn L. Lunetta, Ethan M. Lange, Lisette Stolk, Francesco Cucca, Anna Murray, Fernando Rivadeneira, Michela Traglia, Rebecca D. Jackson, Henry Völzke, John R. B. Perry, Cathy E. Elks, Ozren Polasek, Daniel F. Gudbjartsson, Jenny A. Visser, Albert Hofman, Claudia Langenberg, Andrea D. Coviello, Nora Franceschini, Diego Vozzi, Alexander P. Reiner, Sheila Ulivi, David Schlessinger, Jennifer E. Huffman, Laura M. Yerges-Armstrong, Elisabeth Altmaier, Daniela Toniolo, Jinyan Huang, Cinzia Sala, Patrick Sulem, Chunyan He, Frank B. Hu, Antonis C. Antoniou, Reedik Mägi, David A. Hinds, Jennifer Kriebel, Xin Li, Eric Boerwinkle, Marek Zygmunt, Caterina Barbieri, David J. Porteous, André G. Uitterlinden, Alanna C. Morrison, Joyce Y. Tung, Simin Liu, Carol A. Wang, Kari Stefansson, Megan L. Grove, Melissa Wellons, Doris Stöckl, Nicholas J. Wareham, Lynda M. Rose, Konstantin Strauch, Julie E. Buring, James G. Wilson, Caroline Hayward, Sandosh Padmanabhan, Evelin Mihailov, Alexander Teumer, Craig E. Pennell, Ursula M. Schick, Andres Metspalu, Deborah J. Thompson, Unnur Thorsteinsdottir, Katherine S. Ruth, Uwe Völker, Felix R. Day, Jian'an Luan, Robert A. Scott, Ellen W. Demerath, Ilaria Gandin, and Daniel I. Chasman

Subjects
Genetics, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary, 030220 oncology & carcinogenesis, 030232 urology & nephrology, Menarche, General Physics and Astronomy, General Chemistry, Biology, General Biochemistry, Genetics and Molecular Biology, Genealogy, Coding (social sciences)
Abstract

Nature Communications 6, Article number: 7756 10.1038/ncomms8756 (2015); Published August042015; Updated December172016 In the Results section and in the legend of Table 1 of this Article, the company deCODE genetics, Inc. is incorrectly referred to as ‘Diabetes Epidemiology: collaborative analysis of Diagnostic criteria in Europe'. In neither instance is deCODE an abbreviation.

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6. Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure

Author

Danielle Rasooly, Gina M. Peloso, Alexandre C. Pereira, Hesam Dashti, Claudia Giambartolomei, Eleanor Wheeler, Nay Aung, Brian R. Ferolito, Maik Pietzner, Eric H. Farber-Eger, Quinn Stanton Wells, Nicole M. Kosik, Liam Gaziano, Daniel C. Posner, A. Patrícia Bento, Qin Hui, Chang Liu, Krishna Aragam, Zeyuan Wang, Brian Charest, Jennifer E. Huffman, Peter W. F. Wilson, Lawrence S. Phillips, John Whittaker, Patricia B. Munroe, Steffen E. Petersen, Kelly Cho, Andrew R. Leach, María Paula Magariños, John Michael Gaziano, VA Million Veteran Program, Claudia Langenberg, Yan V. Sun, Jacob Joseph, and Juan P. Casas

Subjects
Science
Abstract

Abstract We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.

Published
2023
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7. Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups

Author

Nuzulul Kurniansyah, Matthew O. Goodman, Alyna T. Khan, Jiongming Wang, Elena Feofanova, Joshua C. Bis, Kerri L. Wiggins, Jennifer E. Huffman, Tanika Kelly, Tali Elfassy, Xiuqing Guo, Walter Palmas, Henry J. Lin, Shih-Jen Hwang, Yan Gao, Kendra Young, Gregory L. Kinney, Jennifer A. Smith, Bing Yu, Simin Liu, Sylvia Wassertheil-Smoller, JoAnn E. Manson, Xiaofeng Zhu, Yii-Der Ida Chen, I-Te Lee, C. Charles Gu, Donald M. Lloyd-Jones, Sebastian Zöllner, Myriam Fornage, Charles Kooperberg, Adolfo Correa, Bruce M. Psaty, Donna K. Arnett, Carmen R. Isasi, Stephen S. Rich, Robert C. Kaplan, Susan Redline, Braxton D. Mitchell, Nora Franceschini, Daniel Levy, Jerome I. Rotter, Alanna C. Morrison, and Tamar Sofer

Subjects
Science
Abstract

Abstract We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

Published
2023
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8. Genomics and phenomics of body mass index reveals a complex disease network

Author

Jie Huang, Jennifer E. Huffman, Yunfeng Huang, Ítalo Do Valle, Themistocles L. Assimes, Sridharan Raghavan, Benjamin F. Voight, Chang Liu, Albert-László Barabási, Rose D. L. Huang, Qin Hui, Xuan-Mai T. Nguyen, Yuk-Lam Ho, Luc Djousse, Julie A. Lynch, Marijana Vujkovic, Catherine Tcheandjieu, Hua Tang, Scott M. Damrauer, Peter D. Reaven, Donald Miller, Lawrence S. Phillips, Maggie C. Y. Ng, Mariaelisa Graff, Christopher A. Haiman, Ruth J. F. Loos, Kari E. North, Loic Yengo, George Davey Smith, Danish Saleheen, J. Michael Gaziano, Daniel J. Rader, Philip S. Tsao, Kelly Cho, Kyong-Mi Chang, Peter W. F. Wilson, VA Million Veteran Program, Yan V. Sun, and Christopher J. O’Donnell

Subjects
Science
Abstract

Elevated body mass index is heritable and associated with many health conditions that impact morbidity and mortality. Here, the authors identify greater than 900 genetic loci for body mass index (BMI) and find over 300 diagnoses associated with increasing BMI.

Published
2022
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9. The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function

Author

J. Allen Bennett, Michael A. Mastrangelo, Sara K. Ture, Charles O. Smith, Shannon G. Loelius, Rachel A. Berg, Xu Shi, Ryan M. Burke, Sherry L. Spinelli, Scott J. Cameron, Thomas E. Carey, Paul S. Brookes, Robert E. Gerszten, Maria Sabater-Lleal, Paul S. de Vries, Jennifer E. Huffman, Nicholas L. Smith, Craig N. Morrell, and Charles J. Lowenstein

Subjects
Science
Abstract

Genetic association studies have identified loci including the choline transporter SLC44A2 as a potential regulator of thrombosis. Here the authors report that loss of SLC44A2 impairs platelet activation and thrombosis in mice via a reduction of mitochondrial ATP production.

Published
2020
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10. Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels

Author

Adrienne Tin, Yong Li, Jennifer A. Brody, Teresa Nutile, Audrey Y. Chu, Jennifer E. Huffman, Qiong Yang, Ming-Huei Chen, Cassianne Robinson-Cohen, Aurélien Macé, Jun Liu, Ayşe Demirkan, Rossella Sorice, Sanaz Sedaghat, Melody Swen, Bing Yu, Sahar Ghasemi, Alexanda Teumer, Peter Vollenweider, Marina Ciullo, Meng Li, André G. Uitterlinden, Robert Kraaij, Najaf Amin, Jeroen van Rooij, Zoltán Kutalik, Abbas Dehghan, Barbara McKnight, Cornelia M. van Duijn, Alanna Morrison, Bruce M. Psaty, Eric Boerwinkle, Caroline S. Fox, Owen M. Woodward, and Anna Köttgen

Subjects
Science
Abstract

Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.

Published
2018
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11. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author

Anne E. Justice, Thomas W. Winkler, Mary F. Feitosa, Misa Graff, Virginia A. Fisher, Kristin Young, Llilda Barata, Xuan Deng, Jacek Czajkowski, David Hadley, Julius S. Ngwa, Tarunveer S. Ahluwalia, Audrey Y. Chu, Nancy L. Heard-Costa, Elise Lim, Jeremiah Perez, John D. Eicher, Zoltán Kutalik, Luting Xue, Anubha Mahajan, Frida Renström, Joseph Wu, Qibin Qi, Shafqat Ahmad, Tamuno Alfred, Najaf Amin, Lawrence F. Bielak, Amelie Bonnefond, Jennifer Bragg, Gemma Cadby, Martina Chittani, Scott Coggeshall, Tanguy Corre, Nese Direk, Joel Eriksson, Krista Fischer, Mathias Gorski, Marie Neergaard Harder, Momoko Horikoshi, Tao Huang, Jennifer E. Huffman, Anne U. Jackson, Johanne Marie Justesen, Stavroula Kanoni, Leena Kinnunen, Marcus E. Kleber, Pirjo Komulainen, Meena Kumari, Unhee Lim, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Rita P. S. Middelberg, Martina Müller-Nurasyid, Pau Navarro, Louis Pérusse, Natalia Pervjakova, Cinzia Sarti, Albert Vernon Smith, Jennifer A. Smith, Alena Stančáková, Rona J. Strawbridge, Heather M. Stringham, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W. van der Laan, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Sailaja L. Vedantam, Niek Verweij, Jacqueline M. Vink, Veronique Vitart, Ying Wu, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Martina E. Zimmermann, Niha Zubair, Gonçalo R. Abecasis, Linda S. Adair, Saima Afaq, Uzma Afzal, Stephan J. L. Bakker, Traci M. Bartz, John Beilby, Richard N. Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Eric Boerwinkle, Lori L. Bonnycastle, Erwin Bottinger, Daniele Braga, Brendan M. Buckley, Steve Buyske, Harry Campbell, John C. Chambers, Francis S. Collins, Joanne E. Curran, Gert J. de Borst, Anton J. M. de Craen, Eco J. C. de Geus, George Dedoussis, Graciela E. Delgado, Hester M. den Ruijter, Gudny Eiriksdottir, Anna L. Eriksson, Tõnu Esko, Jessica D. Faul, Ian Ford, Terrence Forrester, Karl Gertow, Bruna Gigante, Nicola Glorioso, Jian Gong, Harald Grallert, Tanja B. Grammer, Niels Grarup, Saskia Haitjema, Göran Hallmans, Anders Hamsten, Torben Hansen, Tamara B. Harris, Catharina A. Hartman, Maija Hassinen, Nicholas D. Hastie, Andrew C. Heath, Dena Hernandez, Lucia Hindorff, Lynne J. Hocking, Mette Hollensted, Oddgeir L. Holmen, Georg Homuth, Jouke Jan Hottenga, Jie Huang, Joseph Hung, Nina Hutri-Kähönen, Erik Ingelsson, Alan L. James, John-Olov Jansson, Marjo-Riitta Jarvelin, Min A. Jhun, Marit E. Jørgensen, Markus Juonala, Mika Kähönen, Magnus Karlsson, Heikki A. Koistinen, Ivana Kolcic, Genovefa Kolovou, Charles Kooperberg, Bernhard K. Krämer, Johanna Kuusisto, Kirsti Kvaløy, Timo A. Lakka, Claudia Langenberg, Lenore J. Launer, Karin Leander, Nanette R. Lee, Lars Lind, Cecilia M. Lindgren, Allan Linneberg, Stephane Lobbens, Marie Loh, Mattias Lorentzon, Robert Luben, Gitta Lubke, Anja Ludolph-Donislawski, Sara Lupoli, Pamela A. F. Madden, Reija Männikkö, Pedro Marques-Vidal, Nicholas G. Martin, Colin A. McKenzie, Barbara McKnight, Dan Mellström, Cristina Menni, Grant W. Montgomery, AW (Bill) Musk, Narisu Narisu, Matthias Nauck, Ilja M. Nolte, Albertine J. Oldehinkel, Matthias Olden, Ken K. Ong, Sandosh Padmanabhan, Patricia A. Peyser, Charlotta Pisinger, David J. Porteous, Olli T. Raitakari, Tuomo Rankinen, D. C. Rao, Laura J. Rasmussen-Torvik, Rajesh Rawal, Treva Rice, Paul M. Ridker, Lynda M. Rose, Stephanie A. Bien, Igor Rudan, Serena Sanna, Mark A. Sarzynski, Naveed Sattar, Kai Savonen, David Schlessinger, Salome Scholtens, Claudia Schurmann, Robert A. Scott, Bengt Sennblad, Marten A. Siemelink, Günther Silbernagel, P Eline Slagboom, Harold Snieder, Jan A. Staessen, David J. Stott, Morris A. Swertz, Amy J. Swift, Kent D. Taylor, Bamidele O. Tayo, Barbara Thorand, Dorothee Thuillier, Jaakko Tuomilehto, Andre G. Uitterlinden, Liesbeth Vandenput, Marie-Claude Vohl, Henry Völzke, Judith M. Vonk, Gérard Waeber, Melanie Waldenberger, R. G. J. Westendorp, Sarah Wild, Gonneke Willemsen, Bruce H. R. Wolffenbuttel, Andrew Wong, Alan F. Wright, Wei Zhao, M Carola Zillikens, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Carsten A. Böger, Dorret I. Boomsma, Claude Bouchard, Marcel Bruinenberg, Daniel I. Chasman, Yii-DerIda Chen, Peter S. Chines, Richard S. Cooper, Francesco Cucca, Daniele Cusi, Ulf de Faire, Luigi Ferrucci, Paul W. Franks, Philippe Froguel, Penny Gordon-Larsen, Hans- Jörgen Grabe, Vilmundur Gudnason, Christopher A. Haiman, Caroline Hayward, Kristian Hveem, Andrew D. Johnson, J Wouter Jukema, Sharon L. R. Kardia, Mika Kivimaki, Jaspal S. Kooner, Diana Kuh, Markku Laakso, Terho Lehtimäki, Loic Le Marchand, Winfried März, Mark I. McCarthy, Andres Metspalu, Andrew P. Morris, Claes Ohlsson, Lyle J. Palmer, Gerard Pasterkamp, Oluf Pedersen, Annette Peters, Ulrike Peters, Ozren Polasek, Bruce M. Psaty, Lu Qi, Rainer Rauramaa, Blair H. Smith, Thorkild I. A. Sørensen, Konstantin Strauch, Henning Tiemeier, Elena Tremoli, Pim van der Harst, Henrik Vestergaard, Peter Vollenweider, Nicholas J. Wareham, David R. Weir, John B. Whitfield, James F. Wilson, Jessica Tyrrell, Timothy M. Frayling, Inês Barroso, Michael Boehnke, Panagiotis Deloukas, Caroline S. Fox, Joel N. Hirschhorn, David J. Hunter, Tim D. Spector, David P. Strachan, Cornelia M. van Duijn, Iris M. Heid, Karen L. Mohlke, Jonathan Marchini, Ruth J. F. Loos, Tuomas O. Kilpeläinen, Ching-Ti Liu, Ingrid B. Borecki, Kari E. North, and L Adrienne Cupples

Subjects
Science
Abstract

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Published
2017
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12. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author

Janina S. Ried, Janina Jeff M., Audrey Y. Chu, Jennifer L. Bragg-Gresham, Jenny van Dongen, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, Tõnu Esko, Mary F. Feitosa, Anuj Goel, Mathias Gorski, Caroline Hayward, Nancy L. Heard-Costa, Anne U. Jackson, Eero Jokinen, Stavroula Kanoni, Kati Kristiansson, Zoltán Kutalik, Jari Lahti, Jian'an Luan, Reedik Mägi, Anubha Mahajan, Massimo Mangino, Carolina Medina-Gomez, Keri L. Monda, Ilja M. Nolte, Louis Pérusse, Inga Prokopenko, Lu Qi, Lynda M. Rose, Erika Salvi, Megan T. Smith, Harold Snieder, Alena Stančáková, Yun Ju Sung, Ioanna Tachmazidou, Alexander Teumer, Gudmar Thorleifsson, Pim van der Harst, Ryan W. Walker, Sophie R. Wang, Sarah H. Wild, Sara M. Willems, Andrew Wong, Weihua Zhang, Eva Albrecht, Alexessander Couto Alves, Stephan J. L. Bakker, Cristina Barlassina, Traci M. Bartz, John Beilby, Claire Bellis, Richard N. Bergman, Sven Bergmann, John Blangero, Matthias Blüher, Eric Boerwinkle, Lori L. Bonnycastle, Stefan R. Bornstein, Marcel Bruinenberg, Harry Campbell, Yii-Der Ida Chen, Charleston W. K. Chiang, Peter S. Chines, Francis S Collins, Fracensco Cucca, L Adrienne Cupples, Francesca D’Avila, Eco J .C. de Geus, George Dedoussis, Maria Dimitriou, Angela Döring, Johan G. Eriksson, Aliki-Eleni Farmaki, Martin Farrall, Teresa Ferreira, Krista Fischer, Nita G. Forouhi, Nele Friedrich, Anette Prior Gjesing, Nicola Glorioso, Mariaelisa Graff, Harald Grallert, Niels Grarup, Jürgen Gräßler, Jagvir Grewal, Anders Hamsten, Marie Neergaard Harder, Catharina A. Hartman, Maija Hassinen, Nicholas Hastie, Andrew Tym Hattersley, Aki S. Havulinna, Markku Heliövaara, Hans Hillege, Albert Hofman, Oddgeir Holmen, Georg Homuth, Jouke-Jan Hottenga, Jennie Hui, Lise Lotte Husemoen, Pirro G. Hysi, Aaron Isaacs, Till Ittermann, Shapour Jalilzadeh, Alan L. James, Torben Jørgensen, Pekka Jousilahti, Antti Jula, Johanne Marie Justesen, Anne E. Justice, Mika Kähönen, Maria Karaleftheri, Kay Tee Khaw, Sirkka M. Keinanen-Kiukaanniemi, Leena Kinnunen, Paul B. Knekt, Heikki A. Koistinen, Ivana Kolcic, Ishminder K. Kooner, Seppo Koskinen, Peter Kovacs, Theodosios Kyriakou, Tomi Laitinen, Claudia Langenberg, Alexandra M. Lewin, Peter Lichtner, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Roberto Lorbeer, Mattias Lorentzon, Robert Luben, Valeriya Lyssenko, Satu Männistö, Paolo Manunta, Irene Mateo Leach, Wendy L. McArdle, Barbara Mcknight, Karen L. Mohlke, Evelin Mihailov, Lili Milani, Rebecca Mills, May E. Montasser, Andrew P. Morris, Gabriele Müller, Arthur W. Musk, Narisu Narisu, Ken K. Ong, Ben A. Oostra, Clive Osmond, Aarno Palotie, James S. Pankow, Lavinia Paternoster, Brenda W. Penninx, Irene Pichler, Maria G. Pilia, Ozren Polašek, Peter P. Pramstaller, Olli T Raitakari, Tuomo Rankinen, D. C. Rao, Nigel W. Rayner, Rasmus Ribel-Madsen, Treva K. Rice, Marcus Richards, Paul M. Ridker, Fernando Rivadeneira, Kathy A. Ryan, Serena Sanna, Mark A. Sarzynski, Salome Scholtens, Robert A. Scott, Sylvain Sebert, Lorraine Southam, Thomas Hempel Sparsø, Valgerdur Steinthorsdottir, Kathleen Stirrups, Ronald P. Stolk, Konstantin Strauch, Heather M. Stringham, Morris A. Swertz, Amy J. Swift, Anke Tönjes, Emmanouil Tsafantakis, Peter J. van der Most, Jana V. Van Vliet-Ostaptchouk, Liesbeth Vandenput, Erkki Vartiainen, Cristina Venturini, Niek Verweij, Jorma S. Viikari, Veronique Vitart, Marie-Claude Vohl, Judith M. Vonk, Gérard Waeber, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Thomas W. Winkler, Alan F. Wright, Laura M. Yerges-Armstrong, Jing Hua Zhao, M. Carola Zillikens, Dorret I. Boomsma, Claude Bouchard, John C. Chambers, Daniel I. Chasman, Daniele Cusi, Ron T. Gansevoort, Christian Gieger, Torben Hansen, Andrew A. Hicks, Frank Hu, Kristian Hveem, Marjo-Riitta Jarvelin, Eero Kajantie, Jaspal S. Kooner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Timo A. Lakka, Terho Lehtimäki, Andres Metspalu, Inger Njølstad, Claes Ohlsson, Albertine J. Oldehinkel, Lyle J. Palmer, Oluf Pedersen, Markus Perola, Annette Peters, Bruce M. Psaty, Hannu Puolijoki, Rainer Rauramaa, Igor Rudan, Veikko Salomaa, Peter E. H. Schwarz, Alan R. Shudiner, Jan H. Smit, Thorkild I. A. Sørensen, Timothy D. Spector, Kari Stefansson, Michael Stumvoll, Angelo Tremblay, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Uwe Völker, Peter Vollenweider, Nicholas J. Wareham, Hugh Watkins, James F. Wilson, Eleftheria Zeggini, Goncalo R. Abecasis, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Cornelia M. van Duijn, Caroline Fox, Leif C. Groop, Iris M. Heid, David J. Hunter, Robert C. Kaplan, Mark I. McCarthy, Kari E. North, Jeffrey R. O'Connell, David Schlessinger, Unnur Thorsteinsdottir, David P. Strachan, Timothy Frayling, Joel N. Hirschhorn, Martina Müller-Nurasyid, and Ruth J. F. Loos

Subjects
Science
Abstract

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Published
2016
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