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

Publication

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

Journal Paper/Review - Apr 26, 2017

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

Citation

Zhao W, Stott D, Staessen J, Snieder H, Slagboom P, Silbernagel G, Siemelink M, Sennblad B, Scott R, Schurmann C, Scholtens S, Schlessinger D, Savonen K, Sattar N, Sarzynski M, Sanna S, Rudan I, Bien S, Swertz M, Swift A, Taylor K, Wright A, Wong A, Wolffenbuttel B, Willemsen G, Wild S, Westendorp R, Waldenberger M, Waeber G, Vonk J, Völzke H, Vohl M, Vandenput L, Uitterlinden A, Tuomilehto J, Thuillier D, Thorand B, Tayo B, Rose L, Ridker P, Rice T, McKenzie C, Martin N, Marques-Vidal P, Männikkö R, Madden P, Lupoli S, Ludolph-Donislawski A, Lubke G, Luben R, Lorentzon M, Loh M, Lobbens S, Linneberg A, Lindgren C, Lind L, Lee N, Leander K, McKnight B, Mellström D, Menni C, Rawal R, Rasmussen-Torvik L, Rao D, Rankinen T, Raitakari O, Porteous D, Pisinger C, Peyser P, Padmanabhan S, Ong K, Olden M, Oldehinkel A, Nolte I, Nauck M, Narisu N, Musk A, Montgomery G, Launer L, Cupples L, Whitfield J, Weir D, Wareham N, Vollenweider P, Vestergaard H, van der Harst P, Tremoli E, Tiemeier H, Strauch K, Sørensen T, Smith B, Rauramaa R, Qi L, Psaty B, Polasek O, Peters U, Peters A, Wilson J, Tyrrell J, Frayling T, North K, Borecki I, Liu C, Kilpeläinen T, Loos R, Marchini J, Mohlke K, Heid I, van Duijn C, Strachan D, Spector T, Hunter D, Hirschhorn J, Fox C, Deloukas P, Boehnke M, Barroso I, Pedersen O, Pasterkamp G, Palmer L, Froguel P, Franks P, Ferrucci L, Faire U, Cusi D, Cucca F, Cooper R, Chines P, Chen Y, Chasman D, Bruinenberg M, Bouchard C, Boomsma D, Böger C, Bandinelli S, Balkau B, Baldassarre D, Gordon-Larsen P, Grabe H, Gudnason V, Ohlsson C, Morris A, Metspalu A, McCarthy M, März W, Marchand L, Lehtimäki T, Laakso M, Kuh D, Kooner J, Kivimäki M, Kardia S, Wouter Jukema J, Johnson A, Hveem K, Hayward C, Haiman C, Zillikens M, Langenberg C, Zhang W, Pérusse L, Navarro P, Müller-Nurasyid M, Middelberg R, Marten J, Manichaikul A, Mangino M, Lyytikäinen L, Luan J, Lim U, Kumari M, Komulainen P, Kleber M, Kinnunen L, Kanoni S, Justesen J, Jackson A, Pervjakova N, Sarti C, Smith A, Yengo L, Wu Y, Vitart V, Vink J, Verweij N, Vedantam S, van Vliet-Ostaptchouk J, van der Most P, van der Laan S, Trompet S, Teumer A, Tanaka T, Sung Y, Stringham H, Strawbridge R, Stančáková A, Smith J, Huffman J, Huang T, Horikoshi M, Kutalik Z, Eicher J, Perez J, Lim E, Heard-Costa N, Chu A, Ahluwalia T, Ngwa J, Hadley D, Czajkowski J, Deng X, Barata L, Young K, Fisher V, Graff M, Feitosa M, Winkler T, Xue L, Mahajan A, Renström F, Neergaard Harder M, Gorski M, Fischer K, Eriksson J, Direk N, Corre T, Coggeshall S, Chittani M, Cadby G, Bragg J, Bonnefond A, Bielak L, Amin N, Alfred T, Ahmad S, Qi Q, Wu J, Justice A, Lakka T, Homuth G, Holmen O, Hollensted M, Hocking L, Hindorff L, Hernandez D, Heath A, Hastie N, Hassinen M, Hartman C, Harris T, Hansen T, Hamsten A, Hallmans G, Haitjema S, Grarup N, Grammer T, Jan Hottenga J, Huang J, Hung J, Kvaløy K, Kuusisto J, Krämer B, Kooperberg C, Kolovou G, Kolcic I, Koistinen H, Karlsson M, Kähönen M, Juonala M, Jørgensen M, Jhun M, Jarvelin M, Jansson J, James A, Ingelsson E, Hutri-Kähönen N, Grallert H, Gong J, Glorioso N, Braga D, Bottinger E, Bonnycastle L, Boerwinkle E, Blangero J, Biffar R, Bergmann S, Bergman R, Beilby J, Bartz T, Bakker S, Afzal U, Afaq S, Adair L, Abecasis G, Zubair N, Zimmermann M, Buckley B, Buyske S, Campbell H, Gigante B, Gertow K, Forrester T, Ford I, Faul J, Esko T, Eriksson A, Eiriksdottir G, den Ruijter H, Delgado G, Dedoussis G, de Geus E, de Craen A, de Borst G, Curran J, Collins F, Chambers J, Hua Zhao J. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 2017; 8:14977.

Type

Journal Paper/Review (English)

Journal

Nat Commun 2017; 8

Publication Date

Apr 26, 2017

Issn Electronic

2041-1723

Pages

14977

Brief description/objective

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.