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

Authors:
Saima Afaq
Saima Afaq
Institute of Public health and Social Sciences, Khyber medical university Peshawar Pakistan
Dr
Peshawar, KPK | Pakistan
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 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 L Adrienne Cupples

Nat Commun 2017 04 26;8:14977. Epub 2017 Apr 26.

Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.

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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http://dx.doi.org/10.1038/ncomms14977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414044PMC
April 2017
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