Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-26

AUTHORS

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 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, L Adrienne Cupples

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. More... »

PAGES

14977

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    N/A

    VOLUME

    8

    Author Affiliations

  • University of North Carolina System
  • University of Regensburg
  • Washington University in St. Louis
  • Boston University
  • Johns Hopkins University
  • Steno Diabetes Center
  • Brigham and Women's Hospital
  • Boston University School of Medicine
  • National Heart Lung and Blood Institute
  • University of Lausanne
  • Wellcome Centre for Human Genetics
  • Lund University
  • Albert Einstein College of Medicine
  • Harvard University
  • Icahn School of Medicine at Mount Sinai
  • Erasmus University Medical Center
  • University of Michigan–Ann Arbor
  • University of Western Australia
  • University of Milan
  • University of Washington
  • Dokuz Eylül University
  • University of Gothenburg
  • University of Tartu
  • University Hospital Regensburg
  • University of Copenhagen
  • University of Oxford
  • National University of Singapore
  • University of Edinburgh
  • Queen Mary University of London
  • National Institute for Health and Welfare
  • Heidelberg University
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • University College London
  • University of Hawaii at Manoa
  • Institute of Metabolic Science
  • University of Tampere
  • Guy's and St Thomas' NHS Foundation Trust
  • University of Virginia
  • QIMR Berghofer Medical Research Institute
  • German Centre for Cardiovascular Research
  • Université Laval
  • University of Iceland
  • University of Eastern Finland
  • Karolinska University Hospital
  • National Institute on Aging
  • University of Greifswald
  • Leiden University Medical Center
  • University Medical Center Utrecht
  • University Medical Center Groningen
  • Broad Institute
  • Radboud University Nijmegen
  • University of North Carolina at Chapel Hill
  • Ealing Hospital NHS Trust
  • Fred Hutchinson Cancer Research Center
  • University of Southern California
  • The University of Texas Rio Grande Valley
  • The University of Texas Health Science Center at Houston
  • National Human Genome Research Institute
  • University College Cork
  • Rutgers University
  • Imperial College Healthcare NHS Trust
  • VU University Amsterdam
  • Harokopio University
  • Icelandic Heart Association
  • University of Glasgow
  • Karolinska Institute
  • University of Sassari
  • German Center for Diabetes Research
  • Umeå University
  • National Institutes of Health
  • St Olav's University Hospital
  • Wellcome Sanger Institute
  • Sir Charles Gairdner Hospital
  • Uppsala University
  • Oulu University Hospital
  • Turku University Hospital
  • Minerva Foundation
  • University of Split
  • Onassis Cardiac Surgery Center
  • Norwegian University of Science and Technology
  • University of San Carlos
  • Agency for Science, Technology and Research
  • University of Cambridge
  • University of Notre Dame
  • Ludwig Maximilian University of Munich
  • University Hospital of Lausanne
  • King's College London
  • University of Turku
  • Pennington Biomedical Research Center
  • Northwestern University
  • Helmholtz Zentrum München
  • Institute of Genetic and Biomedical Research
  • Medical University of Graz
  • Maastricht University
  • University of California Los Angeles
  • Loyola University Chicago
  • King Abdulaziz University
  • MRC Unit for Lifelong Health and Ageing
  • Centro Cardiologico Monzino
  • Centre for research in epidemiology and population health
  • Harbor–UCLA Medical Center
  • Institute of Biomedical Technologies
  • Imperial College London
  • German Center for Neurodegenerative Diseases
  • Netherlands Heart Institute
  • Churchill Hospital
  • University of Liverpool
  • University of Adelaide
  • Group Health Cooperative
  • Tulane University
  • Kuopio University Hospital
  • University of Bristol
  • University of Exeter
  • Wageningen University & Research
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms14977

    DOI

    http://dx.doi.org/10.1038/ncomms14977

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085060523

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28443625


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