Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Authors: Justice Anne E. , Winkler Thomas W. , Feitosa Mary F. , Graff Misa , Fisher Virginia A. , Young Kristin , Barata Llilda , Deng Xuan , Czajkowski Jacek , Hadley David , Ngwa Julius S. , Ahluwalia Tarunveer S. , Chu Audrey Y. , Heard-Costa Nancy L. , Lim Elise , Perez Jeremiah , Eicher John D. , Kutalik Zoltán , Xue Luting , Mahajan Anubha , Renström Frida , Wu Joseph , Qi Qibin , Ahmad Shafqat , Alfred Tamuno , Amin Najaf , Bielak Lawrence F. , Bonnefond Amelie , Bragg Jennifer , Cadby Gemma , Chittani Martina , Coggeshall Scott , Corre Tanguy , Direk Nese , Eriksson Joel , Fischer Krista , Gorski Mathias , Neergaard Harder Marie , Horikoshi Momoko , Huang Tao , Huffman Jennifer E. , Jackson Anne U. , Justesen Johanne Marie , Kanoni Stavroula , Kinnunen Leena , Kleber Marcus E. , Komulainen Pirjo , Kumari Meena , Lim Unhee , Luan Jian'an , Lyytikäinen Leo-Pekka , Mangino Massimo , Manichaikul Ani , Marten Jonathan , Middelberg Rita P. S. , Müller-Nurasyid Martina , Navarro Pau , Pérusse Louis , Pervjakova Natalia , Sarti Cinzia , Smith Albert Vernon , Smith Jennifer A. , Stančáková Alena , Strawbridge Rona J. , Stringham Heather M. , Sung Yun Ju , Tanaka Toshiko , Teumer Alexander , Trompet Stella , van der Laan Sander W. , van der Most Peter J. , Van Vliet-Ostaptchouk Jana V. , Vedantam Sailaja L. , Verweij Niek , Vink Jacqueline M. , Vitart Veronique , Wu Ying , Yengo Loic , Zhang Weihua , Hua Zhao Jing , Zimmermann Martina E. , Zubair Niha , Abecasis Gonçalo R. , Adair Linda S. , Afaq Saima , Afzal Uzma , Bakker Stephan J. L. , Bartz Traci M. , Beilby John , Bergman Richard N. , Bergmann Sven , Biffar Reiner , Blangero John , Boerwinkle Eric , Bonnycastle Lori L. , Bottinger Erwin , Braga Daniele , Buckley Brendan M. , Buyske Steve , Campbell Harry , Chambers John C. , Collins Francis S. , Curran Joanne E. , de Borst Gert J. , de Craen Anton J. M. , de Geus Eco J. C. , Dedoussis George , Delgado Graciela E. , den Ruijter Hester M. , Eiriksdottir Gudny , Eriksson Anna L. , Esko Tõnu , Faul Jessica D. , Ford Ian , Forrester Terrence , Gertow Karl , Gigante Bruna , Glorioso Nicola , Gong Jian , Grallert Harald , Grammer Tanja B. , Grarup Niels , Haitjema Saskia , Hallmans Göran , Hamsten Anders , Hansen Torben , Harris Tamara B. , Hartman Catharina A. , Hassinen Maija , Hastie Nicholas D. , Heath Andrew C. , Hernandez Dena , Hindorff Lucia , Hocking Lynne J. , Hollensted Mette , Holmen Oddgeir L. , Homuth Georg , Jan Hottenga Jouke , Huang Jie , Hung Joseph , Hutri-Kähönen Nina , Ingelsson Erik , James Alan L. , Jansson John-Olov , Jarvelin Marjo-Riitta , Jhun Min A. , Jørgensen Marit E. , Juonala Markus , Kähönen Mika , Karlsson Magnus , Koistinen Heikki A. , Kolcic Ivana , Kolovou Genovefa , Kooperberg Charles , Krämer Bernhard K. , Kuusisto Johanna , Kvaløy Kirsti , Lakka Timo A. , Langenberg Claudia , Launer Lenore J. , Leander Karin , Lee Nanette R. , Lind Lars , Lindgren Cecilia M. , Linneberg Allan , Lobbens Stephane , Loh Marie , Lorentzon Mattias , Luben Robert , Lubke Gitta , Ludolph-Donislawski Anja , Lupoli Sara , Madden Pamela A. F. , Männikkö Reija , Marques-Vidal Pedro , Martin Nicholas G. , McKenzie Colin A. , McKnight Barbara , Mellström Dan , Menni Cristina , Montgomery Grant W. , Musk AW , Narisu Narisu , Nauck Matthias , Nolte Ilja M. , Oldehinkel Albertine J. , Olden Matthias , Ong Ken K. , Padmanabhan Sandosh , Peyser Patricia A. , Pisinger Charlotta , Porteous David J. , Raitakari Olli T. , Rankinen Tuomo , Rao D. C. , Rasmussen-Torvik Laura J. , Rawal Rajesh , Rice Treva , Ridker Paul M. , Rose Lynda M. , Bien Stephanie A. , Rudan Igor , Sanna Serena , Sarzynski Mark A. , Sattar Naveed , Savonen Kai , Schlessinger David , Scholtens Salome , Schurmann Claudia , Scott Robert A. , Sennblad Bengt , Siemelink Marten A. , Silbernagel Günther , Slagboom P Eline , Snieder Harold , Staessen Jan A. , Stott David J. , Swertz Morris A. , Swift Amy J. , Taylor Kent D. , Tayo Bamidele O. , Thorand Barbara , Thuillier Dorothee , Tuomilehto Jaakko , Uitterlinden Andre G. , Vandenput Liesbeth , Vohl Marie-Claude , Völzke Henry , Vonk Judith M. , Waeber Gérard , Waldenberger Melanie , Westendorp R. G. J. , Wild Sarah , Willemsen Gonneke , Wolffenbuttel Bruce H. R. , Wong Andrew , Wright Alan F. , Zhao Wei , Zillikens M Carola , Baldassarre Damiano , Balkau Beverley , Bandinelli Stefania , Böger Carsten A. , Boomsma Dorret I. , Bouchard Claude , Bruinenberg Marcel , Chasman Daniel I. , Chen Yii-DerIda , Chines Peter S. , Cooper Richard S. , Cucca Francesco , Cusi Daniele , Faire Ulf de , Ferrucci Luigi , Franks Paul W. , Froguel Philippe , Gordon-Larsen Penny , Grabe Hans- Jörgen , Gudnason Vilmundur , Haiman Christopher A. , Hayward Caroline , Hveem Kristian , Johnson Andrew D. , Wouter Jukema J , Kardia Sharon L. R. , Kivimaki Mika , Kooner Jaspal S. , Kuh Diana , Laakso Markku , Lehtimäki Terho , Marchand Loic Le , März Winfried , McCarthy Mark I. , Metspalu Andres , Morris Andrew P. , Ohlsson Claes , Palmer Lyle J. , Pasterkamp Gerard , Pedersen Oluf , Peters Annette , Peters Ulrike , Polasek Ozren , Psaty Bruce M. , Qi Lu , Rauramaa Rainer , Smith Blair H. , Sørensen Thorkild I. A. , Strauch Konstantin , Tiemeier Henning , Tremoli Elena , van der Harst Pim , Vestergaard Henrik , Vollenweider Peter , Wareham Nicholas J. , Weir David R. , Whitfield John B. , Wilson James F. , Tyrrell Jessica , Frayling Timothy M. , Barroso Inês , Boehnke Michael , Deloukas Panagiotis , Fox Caroline S. , Hirschhorn Joel N. , Hunter David J. , Spector Tim D. , Strachan David P. , van Duijn Cornelia M. , Heid Iris M. , Mohlke Karen L. , Marchini Jonathan , Loos Ruth J. F. , Kilpeläinen Tuomas O. , Liu Ching-Ti , Borecki Ingrid B. , North Kari E. , Cupples L Adrienne 
Published: April 2017

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.