Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Anne E. Justice(University of North Carolina at Chapel Hill), Thomas W. Winkler(University of Regensburg), Mary F. Feitosa(Washington University in St. Louis), Misa Graff(University of North Carolina at Chapel Hill), Virginia Fisher(Boston University), Kristin L. Young(University of North Carolina at Chapel Hill), Llilda Barata(Washington University in St. Louis), Xuan Deng(Boston University), Jacek Czajkowski(Washington University in St. Louis), David Hadley(St George's, University of London), Julius S. Ngwa(Boston University), Tarunveer S. Ahluwalia(University of Copenhagen), Audrey Y. Chu(Brigham and Women's Hospital), Nancy L. Heard‐Costa(Boston University), Elise Lim(Boston University), Jeremiah Perez(Boston University), John D. Eicher(National Heart Lung and Blood Institute), Zoltán Kutalik(SIB Swiss Institute of Bioinformatics), Luting Xue(Boston University), Anubha Mahajan(Centre for Human Genetics), Frida Renström(Lund University), Joseph Wu(Boston University), Qibin Qi(Albert Einstein College of Medicine), Shafqat Ahmad(Brigham and Women's Hospital), Alfred Tamuno(Icahn School of Medicine at Mount Sinai), Najaf Amin(Erasmus MC), Lawrence F. Bielak(University of Michigan), Amélie Bonnefond(Centre National de la Recherche Scientifique), Jennifer Bragg(University of Michigan), Gemma Cadby(The University of Western Australia), Martina Chittani(University of Milan), Scott Coggeshall(University of Washington), Tanguy Corre(SIB Swiss Institute of Bioinformatics), Neşe Direk(Dokuz Eylül University), Joel Eriksson(University of Gothenburg), Krista Fischer(University of Tartu), Mathias Gorski(University Hospital Regensburg), Marie Neergaard Harder(University of Copenhagen), Momoko Horikoshi(Centre for Human Genetics), Tao Huang(Harvard University), Jennifer E. Huffman(National Heart Lung and Blood Institute), Anne Jackson(University of Michigan), Johanne Marie Justesen(University of Copenhagen), Stavroula Kanoni(Queen Mary University of London), Leena Kinnunen(Finnish Institute for Health and Welfare), Marcus E. Kleber(Heidelberg University), Pirjo Komulainen(University of Eastern Finland), Meena Kumari(University of Essex), Unhee Lim(University of Hawaiʻi at Mānoa), Jian’an Luan(University of Cambridge), Leo‐Pekka Lyytikäinen(Tampere University), Massimo Mangino(King's College London), Ani Manichaikul(University of Virginia Health System), Jonathan Marten(Institute of Genetics and Cancer), Rita P. S. Middelberg(QIMR Berghofer Medical Research Institute), Martina Müller‐Nurasyid(Helmholtz Zentrum München), Pau Navarro(Institute of Genetics and Cancer), Louis Përusse(Université Laval), Natalia Pervjakova(University of Tartu), Cinzia Sarti(City of Helsinki), Albert V. Smith(University of Iceland), Jennifer A. Smith(University of Michigan), Alena Stančáková(University of Eastern Finland), Rona J. Strawbridge(Karolinska University Hospital), Heather M. Stringham(University of Michigan), Yun Ju Sung(Washington University in St. Louis), Toshiko Tanaka(National Institute on Aging), Alexander Teumer(Universitätsmedizin Greifswald), Stella Trompet(Leiden University Medical Center), Sander W. van der Laan(University Medical Center Utrecht), Peter J. van der Most(University Medical Center Groningen), Jana V. van Vliet‐Ostaptchouk(University Medical Center Groningen), Sailaja Vedantam(Broad Institute), Niek Verweij(University Medical Center Groningen), Jacqueline M. Vink(Radboud University Nijmegen), Véronique Vitart(Institute of Genetics and Cancer), Ying Wu(University of North Carolina at Chapel Hill), Loïc Yengo(Centre National de la Recherche Scientifique), Weihua Zhang(Ealing Hospital), Wei Zhao(University of Cambridge), Martina E. Zimmermann(University of Regensburg), Niha Zubair(Fred Hutch Cancer Center), Gonçalo R. Abecasis(University of Michigan), Linda S. Adair(University of North Carolina at Chapel Hill), Saima Afaq(Ealing Hospital), Uzma Afzal(Ealing Hospital), Stephan J. L. Bakker(University Medical Center Groningen), Traci M. Bartz(University of Washington), John Beilby(The University of Western Australia), Richard N. Bergman(Cedars-Sinai Medical Center), Sven Bergmann(SIB Swiss Institute of Bioinformatics), Reiner Biffar(Universitätsmedizin Greifswald), John Blangero(The University of Texas Rio Grande Valley), Eric Boerwinkle(The University of Texas Health Science Center at Houston), Lori L. Bonnycastle(National Human Genome Research Institute), Erwin P. Böttinger(Icahn School of Medicine at Mount Sinai), Daniele Braga(University of Milan), Brendan M. Buckley(University College Cork), Steven Buyske(Rutgers, The State University of New Jersey), Harry Campbell(University of Edinburgh), John C. Chambers(Imperial College Healthcare NHS Trust), Francis S. Collins(National Human Genome Research Institute), Joanne E. Curran(The University of Texas Rio Grande Valley), Gert J. de Borst(University Medical Center Utrecht), Anton J. M. de Craen(Leiden University Medical Center), Eco J. C. de Geus(Vrije Universiteit Brussel), George Dedoussis(Harokopio University of Athens), Graciela E. Delgado(Heidelberg University), Hester M. den Ruijter(University Medical Center Utrecht), Guðný Eiríksdóttir(Icelandic Heart Association), Anna L. Eriksson(University of Gothenburg), Tõnu Esko(Broad Institute), Jessica D. Faul(University of Michigan), Ian Ford(University of Glasgow), Terrence Forrester(University of the West Indies System), Karl Gertow(Karolinska University Hospital), Bruna Gigante(Karolinska Institutet), Nicola Glorioso(University of Sassari), Jian Gong(Fred Hutch Cancer Center), Harald Grallert(Helmholtz Zentrum München), Tanja B. Grammer(Heidelberg University), Niels Grarup(University of Copenhagen), Saskia Haitjema(University Medical Center Utrecht), Göran Hallmans(Umeå University), Anders Hamsten(Karolinska University Hospital), Torben Hansen(University of Copenhagen), Tamara B. Harris(National Institutes of Health), Catharina A. Hartman(University Medical Center Groningen), Maija Hassinen(University of Eastern Finland), Nicholas D. Hastie(Institute of Genetics and Cancer), Andrew C. Heath(Washington University in St. Louis), Dena Hernández(National Institute on Aging), Lucia A. Hindorff(National Institutes of Health), Lynne J. Hocking(University of Aberdeen), Mette Hollensted(University of Copenhagen), Oddgeir L. Holmen(St Olav's University Hospital), Georg Homuth(Universitätsmedizin Greifswald), Jouke Jan Hottenga(Vrije Universiteit Amsterdam), Jie Huang(Wellcome Sanger Institute), Joseph Hung(The University of Western Australia), Nina Hutri‐Kähönen(Tampere University), Erik Ingelsson(Uppsala University), Alan L. James(The University of Western Australia), John-Olov Jansson(University of Gothenburg), Marjo‐Riitta Järvelin(Oulu University Hospital), Min A. Jhun(University of Michigan), Marit E. Jørgensen(Steno Diabetes Centers), Markus Juonala(University of Turku), Mika Kähönen(Tampere University), Magnus K. Karlsson(Lund University), Heikki A. Koistinen(Helsinki University Hospital), Ivana Kolčić(University of Split), Genovefa Kolovou(Onassis Cardiac Surgery Center), Charles Kooperberg(Fred Hutch Cancer Center), Bernhard K. Krämer(Heidelberg University), Johanna Kuusisto(University of Eastern Finland), Kirsti Kvaløy(Norwegian University of Science and Technology), Timo A. Lakka(University of Eastern Finland), Claudia Langenberg(University of Cambridge), Lenore J. Launer(National Institutes of Health), Karin Leander(Karolinska Institutet), Sang Lee(University of San Carlos), Lars Lind(Uppsala University), Cecilia M. Lindgren(Centre for Human Genetics), Allan Linneberg(University of Copenhagen), Stéphane Lobbens(Centre National de la Recherche Scientifique), Marie Loh(Agency for Science, Technology and Research), Mattias Lorentzon(University of Gothenburg), Robert Luben(University of Cambridge), Gitta H. Lubke(University of Notre Dame), Anja Ludolph-Donislawski(Zimmer Biomet (Netherlands)), Sara Lupoli(University of Milan), Pamela A. F. Madden(Washington University in St. Louis), Reija Männikkö(University of Eastern Finland), Pedro Marques‐Vidal(University of Lausanne), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Colin A. McKenzie(University of the West Indies System), Barbara McKnight(University of Washington), Dan Mellström(University of Gothenburg), Cristina Menni(King's College London), Grant W. Montgomery(QIMR Berghofer Medical Research Institute), AW Musk(Karolinska University Hospital), Narisu Narisu(National Human Genome Research Institute), Matthias Nauck(Universitätsmedizin Greifswald), Ilja M. Nolte(University Medical Center Groningen), Albertine J. Oldehinkel(University Medical Center Groningen), Matthias Olden(University of Regensburg), Ken K. Ong(University of Cambridge), Sandosh Padmanabhan(Edinburgh Cancer Research), Patricia A. Peyser(University of Michigan), Charlotta Pisinger(University of Copenhagen), David J. Porteous(Edinburgh Cancer Research), Olli T. Raitakari(University of Turku), Tuomo Rankinen(Pennington Biomedical Research Center), D. C. Rao(Washington University in St. Louis), Laura J. Rasmussen‐Torvik(Northwestern University), Rajesh Rawal(Helmholtz Zentrum München), Treva Rice(Washington University in St. Louis), Paul M. Ridker(Brigham and Women's Hospital), Lynda M. Rose(Brigham and Women's Hospital), Stephanie A. Bien(Fred Hutch Cancer Center), Igor Rudan(University of Edinburgh), Serena Sanna(Institute of Genetic and Biomedical Research), Mark A. Sarzynski(Pennington Biomedical Research Center), Naveed Sattar, Kai Savonen(University of Eastern Finland), David Schlessinger(National Institutes of Health), Salome Scholtens(University Medical Center Groningen), Claudia Schurmann(Icahn School of Medicine at Mount Sinai), Robert A. Scott(University of Cambridge), Bengt Sennblad(Karolinska University Hospital), Marten A. Siemelink(University Medical Center Utrecht), Günther Silbernagel(Medical University of Graz), P. Eline Slagboom(Leiden University Medical Center), Harold Snieder(University Medical Center Groningen), Jan A. Staessen(Maastricht University), David J. Stott(University of Glasgow), Morris A. Swertz(University Medical Center Groningen), Amy J. Swift(National Human Genome Research Institute), Kent D. Taylor(University of California, Los Angeles), Bamidele O. Tayo(Loyola University Chicago), Barbara Thorand(Helmholtz Zentrum München), Dorothée Thuillier(Centre National de la Recherche Scientifique), Jaakko Tuomilehto(Universität für Weiterbildung Krems), André G. Uitterlinden(Erasmus MC), Liesbeth Vandenput(University of Gothenburg), Marie‐Claude Vohl(Université Laval), Henry Völzke(Universitätsmedizin Greifswald), Judith M. Vonk(University Medical Center Groningen), Gérard Waeber(University of Lausanne), Mélanie Waldenberger(Helmholtz Zentrum München), Rudi G. J. Westendorp(University of Copenhagen), Sarah H. Wild(University of Edinburgh), Gonneke Willemsen(Vrije Universiteit Amsterdam), Bruce H. R. Wolffenbuttel(University Medical Center Groningen), Andrew Wong(MRC Unit for Lifelong Health and Ageing), Alan F. Wright(Institute of Genetics and Cancer), Wei Zhao(University of Michigan), M. Carola Zillikens(Erasmus MC), Damiano Baldassarre(University of Milan), Beverley Balkau(Inserm), Stefania Bandinelli(Azienda Usl Toscana Centro), Carsten A. Böger(University Hospital Regensburg), Dorret I. Boomsma(Vrije Universiteit Amsterdam), Claude Bouchard(Pennington Biomedical Research Center), Marcel Bruinenberg(Dialyse Centrum Groningen), Daniel I. Chasman(Brigham and Women's Hospital), Yii-DerIda Chen(The Lundquist Institute), Peter S. Chines(National Human Genome Research Institute), Richard S. Cooper(Loyola University Chicago), Francesco Cucca(University of Sassari), Daniele Cusi(Institute of Biomedical Technologies), Ulf dé Fairé(Karolinska Institutet), Luigi Ferrucci(National Institute on Aging), Paul W. Franks(Harvard University), Philippe Froguel(Centre National de la Recherche Scientifique), Penny Gordon‐Larsen(University of North Carolina at Chapel Hill), Hans J. Grabe(Universitätsmedizin Greifswald), Vilmundur Guðnason(University of Iceland), Christopher A. Haiman(University of Southern California), Caroline Hayward(Edinburgh Cancer Research), Kristian Hveem(Norwegian University of Science and Technology), Andrew D. Johnson(National Heart Lung and Blood Institute), J. Wouter Jukema(Leiden University Medical Center), Sharon L. R. Kardia(University of Michigan), Mika Kivimäki(University College London), Jaspal S. Kooner(Imperial College Healthcare NHS Trust), Diana Kuh(MRC Unit for Lifelong Health and Ageing), Markku Laakso(University of Eastern Finland), Terho Lehtimäki(Tampere University), Loı̈c Le Marchand(University of Hawaiʻi at Mānoa), Winfried März(Medical University of Graz), Mark I. McCarthy(Centre for Human Genetics), Andres Metspalu(University of Tartu), Andrew P. Morris(Centre for Human Genetics), Claes Ohlsson(University of Gothenburg), Lyle J. Palmer(The University of Adelaide), Gerard Pasterkamp(Utrecht University), Oluf Pedersen(University of Copenhagen), Annette Peters(Helmholtz Zentrum München), Ulrike Peters(Fred Hutch Cancer Center), Ozren Polašek(University of Split), Bruce M. Psaty(Group Health Cooperative), Lu Qi(Tulane University), Rainer Rauramaa(University of Eastern Finland), Blair H. Smith(Ninewells Hospital), Thorkild I. A. Sørensen(University of Copenhagen), Konstantin Strauch(Zimmer Biomet (Netherlands)), Henning Tiemeier(Erasmus MC), Elena Tremoli(University of Milan), Pim van der Harst(University Medical Center Groningen), Henrik Vestergaard(University of Copenhagen), Péter Vollenweider(University of Lausanne), Nicholas J. Wareham(University of Cambridge), David R. Weir(University of Michigan), John B. Whitfield(QIMR Berghofer Medical Research Institute), James F. Wilson(Institute of Genetics and Cancer), Jessica Tyrrell(University of Exeter), Timothy M. Frayling(University of Exeter), Inês Barroso(Wellcome Sanger Institute), Michael Boehnke(University of Michigan), Panagiotis Deloukas(Queen Mary University of London), Caroline S. Fox(Framingham Heart Study), Joel N. Hirschhorn(Broad Institute), David J. Hunter(Broad Institute), Tim D. Spector(King's College London), David P. Strachan(St George's, University of London), Cornelia M. van Duijn(Erasmus MC), Iris M. Heid(Helmholtz Zentrum München), Karen L. Mohlke(University of North Carolina at Chapel Hill), Jonathan Marchini(University of Oxford), Ruth J. F. Loos(University of Cambridge), Tuomas O. Kilpeläinen(University of Copenhagen), Ching‐Ti Liu(Boston University), Ingrid B. Borecki(Washington University in St. Louis), Kari E. North(University of North Carolina at Chapel Hill), L. Adrienne Cupples(Boston University)
Cited by 232Open Access
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.
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