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

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 & 297 others 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 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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number14977
Pages (from-to)1-19
Number of pages19
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 26 Apr 2017

Fingerprint

obesity
genome
loci
Meta-Analysis
Obesity
Genes
Genome-Wide Association Study
Smoking
Adiposity
Genome
Association reactions
Addictive Behavior
Body Fat Distribution
Genetic Loci
Oxidative stress
Waist-Hip Ratio
Tobacco
Environmental Exposure
Waist Circumference
Genetic Predisposition to Disease

Keywords

  • Journal Article
  • Epidemiology
  • genetics research
  • genome-wide association studies
  • obesity

Cite this

Justice, A. E., Winkler, T. W., Feitosa, M. F., Graff, M., Fisher, V. A., Young, K., ... Cupples, L. A. (2017). Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nature Communications, 8, 1-19. [14977]. https://doi.org/10.1038/ncomms14977

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

In: Nature Communications, Vol. 8, 14977, 26.04.2017, p. 1-19.

Research output: Contribution to journalArticle

Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, VA, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renström, F, Wu, J, Qi, Q, Ahmad, S, Alfred, T, Amin, N, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Neergaard Harder, M, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikäinen, L-P, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Müller-Nurasyid, M, Navarro, P, Pérusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stančáková, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, Van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N, Vink, JM, Vitart, V, Wu, Y, Yengo, L, Zhang, W, Hua Zhao, J, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Jan Hottenga, J, Huang, J, Hung, J, Hutri-Kähönen, N, Ingelsson, E, James, AL, Jansson, J-O, Jarvelin, M-R, Jhun, MA, Jørgensen, ME, Juonala, M, Kähönen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Krämer, BK, Kuusisto, J, Kvaløy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Männikkö, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellström, D, Menni, C, Montgomery, GW, Musk, AB, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, S, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE, Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, AG, Vandenput, L, Vohl, M-C, Völzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, MC, Baldassarre, D, Balkau, B, Bandinelli, S, Böger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, Y-D, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, Faire, UD, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, H-J, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Wouter Jukema, J, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimäki, T, Marchand, LL, März, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sørensen, TIA, Strauch, K, Tiemeier, H, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, van Duijn, CM, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpeläinen, TO, Liu, C-T, Borecki, IB, North, KE & Cupples, LA 2017, 'Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits', Nature Communications, vol. 8, 14977, pp. 1-19. https://doi.org/10.1038/ncomms14977
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 Bill ; 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. / Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. In: Nature Communications. 2017 ; Vol. 8. pp. 1-19.
@article{4b18a70bd3a84f3db935a6836f9fa1bc,
title = "Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits",
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.",
keywords = "Journal Article, Epidemiology, genetics research, genome-wide association studies, obesity",
author = "Justice, {Anne E} and Winkler, {Thomas W} and Feitosa, {Mary F} and Misa Graff and Fisher, {Virginia A} and Kristin Young and Llilda Barata and Xuan Deng and Jacek Czajkowski and David Hadley and Ngwa, {Julius S} and Ahluwalia, {Tarunveer S} and Chu, {Audrey Y} and Heard-Costa, {Nancy L} and Elise Lim and Jeremiah Perez and Eicher, {John D} and Zolt{\'a}n Kutalik and Luting Xue and Anubha Mahajan and Frida Renstr{\"o}m and Joseph Wu and Qibin Qi and Shafqat Ahmad and Tamuno Alfred and Najaf Amin and Bielak, {Lawrence F} and Amelie Bonnefond and Jennifer Bragg and Gemma Cadby and Martina Chittani and Scott Coggeshall and Tanguy Corre and Nese Direk and Joel Eriksson and Krista Fischer and Mathias Gorski and {Neergaard Harder}, Marie and Momoko Horikoshi and Tao Huang and Huffman, {Jennifer E} and Jackson, {Anne U} and Justesen, {Johanne Marie} and Stavroula Kanoni and Leena Kinnunen and Kleber, {Marcus E} and Pirjo Komulainen and Meena Kumari and Unhee Lim and Jian'an Luan and Leo-Pekka Lyytik{\"a}inen and Massimo Mangino and Ani Manichaikul and Jonathan Marten and Middelberg, {Rita P S} and Martina M{\"u}ller-Nurasyid and Pau Navarro and Louis P{\'e}russe and Natalia Pervjakova and Cinzia Sarti and Smith, {Albert Vernon} and Smith, {Jennifer A} and Alena Stanč{\'a}kov{\'a} and Strawbridge, {Rona J} and Stringham, {Heather M} and Sung, {Yun Ju} and Toshiko Tanaka and Alexander Teumer and Stella Trompet and {van der Laan}, {Sander W} and {van der Most}, {Peter J} and {Van Vliet-Ostaptchouk}, {Jana V} and Vedantam, {Sailaja L} and Niek Verweij and Vink, {Jacqueline M} and Veronique Vitart and Ying Wu and Loic Yengo and Weihua Zhang and {Hua Zhao}, Jing and Zimmermann, {Martina E} and Niha Zubair and Abecasis, {Gon{\cc}alo R} and Adair, {Linda S} and Saima Afaq and Uzma Afzal and Bakker, {Stephan J L} and Bartz, {Traci M} and John Beilby and Bergman, {Richard N} and Sven Bergmann and Reiner Biffar and John Blangero and Eric Boerwinkle and Bonnycastle, {Lori L} and Erwin Bottinger and Daniele Braga and Buckley, {Brendan M} and Steve Buyske and Harry Campbell and Chambers, {John C} and Collins, {Francis S} and Curran, {Joanne E} and {de Borst}, {Gert J} and {de Craen}, {Anton J M} and {de Geus}, {Eco J C} and George Dedoussis and Delgado, {Graciela E} and {den Ruijter}, {Hester M} and Gudny Eiriksdottir and Eriksson, {Anna L} and T{\~o}nu Esko and Faul, {Jessica D} and Ian Ford and Terrence Forrester and Karl Gertow and Bruna Gigante and Nicola Glorioso and Jian Gong and Harald Grallert and Grammer, {Tanja B} and Niels Grarup and Saskia Haitjema and G{\"o}ran Hallmans and Anders Hamsten and Torben Hansen and Harris, {Tamara B} and Hartman, {Catharina A} and Maija Hassinen and Hastie, {Nicholas D} and Heath, {Andrew C} and Dena Hernandez and Lucia Hindorff and Hocking, {Lynne J} and Mette Hollensted and Holmen, {Oddgeir L} and Georg Homuth and {Jan Hottenga}, Jouke and Jie Huang and Joseph Hung and Nina Hutri-K{\"a}h{\"o}nen and Erik Ingelsson and James, {Alan L} and John-Olov Jansson and Marjo-Riitta Jarvelin and Jhun, {Min A} and J{\o}rgensen, {Marit E} and Markus Juonala and Mika K{\"a}h{\"o}nen and Magnus Karlsson and Koistinen, {Heikki A} and Ivana Kolcic and Genovefa Kolovou and Charles Kooperberg and Kr{\"a}mer, {Bernhard K} and Johanna Kuusisto and Kirsti Kval{\o}y and Lakka, {Timo A} and Claudia Langenberg and Launer, {Lenore J} and Karin Leander and Lee, {Nanette R} and Lars Lind and Lindgren, {Cecilia M} and Allan Linneberg and Stephane Lobbens and Marie Loh and Mattias Lorentzon and Robert Luben and Gitta Lubke and Anja Ludolph-Donislawski and Sara Lupoli and Madden, {Pamela A F} and Reija M{\"a}nnikk{\"o} and Pedro Marques-Vidal and Martin, {Nicholas G} and McKenzie, {Colin A} and Barbara McKnight and Dan Mellstr{\"o}m and Cristina Menni and Montgomery, {Grant W} and Musk, {Aw Bill} and Narisu Narisu and Matthias Nauck and Nolte, {Ilja M} and Oldehinkel, {Albertine J} and Matthias Olden and Ong, {Ken K} and Sandosh Padmanabhan and Peyser, {Patricia A} and Charlotta Pisinger and Porteous, {David J} and Raitakari, {Olli T} and Tuomo Rankinen and Rao, {D C} and Rasmussen-Torvik, {Laura J} and Rajesh Rawal and Treva Rice and Ridker, {Paul M} and Rose, {Lynda M} and Bien, {Stephanie A} and Igor Rudan and Serena Sanna and Sarzynski, {Mark A} and Naveed Sattar and Kai Savonen and David Schlessinger and Salome Scholtens and Claudia Schurmann and Scott, {Robert A} and Bengt Sennblad and Siemelink, {Marten A} and G{\"u}nther Silbernagel and Slagboom, {P Eline} and Harold Snieder and Staessen, {Jan A} and Stott, {David J} and Swertz, {Morris A} and Swift, {Amy J} and Taylor, {Kent D} and Tayo, {Bamidele O} and Barbara Thorand and Dorothee Thuillier and Jaakko Tuomilehto and Uitterlinden, {Andre G} and Liesbeth Vandenput and Marie-Claude Vohl and Henry V{\"o}lzke and Vonk, {Judith M} and G{\'e}rard Waeber and Melanie Waldenberger and Westendorp, {R G J} and Sarah Wild and Gonneke Willemsen and Wolffenbuttel, {Bruce H R} and Andrew Wong and Wright, {Alan F} and Wei Zhao and Zillikens, {M Carola} and Damiano Baldassarre and Beverley Balkau and Stefania Bandinelli and B{\"o}ger, {Carsten A} and Boomsma, {Dorret I} and Claude Bouchard and Marcel Bruinenberg and Chasman, {Daniel I} and Yii-DerIda Chen and Chines, {Peter S} and Cooper, {Richard S} and Francesco Cucca and Daniele Cusi and Faire, {Ulf de} and Luigi Ferrucci and Franks, {Paul W} and Philippe Froguel and Penny Gordon-Larsen and Hans-J{\"o}rgen Grabe and Vilmundur Gudnason and Haiman, {Christopher A} and Caroline Hayward and Kristian Hveem and Johnson, {Andrew D} and {Wouter Jukema}, J and Kardia, {Sharon L R} and Mika Kivimaki and Kooner, {Jaspal S} and Diana Kuh and Markku Laakso and Terho Lehtim{\"a}ki and Marchand, {Loic Le} and Winfried M{\"a}rz and McCarthy, {Mark I} and Andres Metspalu and Morris, {Andrew P} and Claes Ohlsson and Palmer, {Lyle J} and Gerard Pasterkamp and Oluf Pedersen and Annette Peters and Ulrike Peters and Ozren Polasek and Psaty, {Bruce M} and Lu Qi and Rainer Rauramaa and Smith, {Blair H} and S{\o}rensen, {Thorkild I A} and Konstantin Strauch and Henning Tiemeier and Elena Tremoli and {van der Harst}, Pim and Henrik Vestergaard and Peter Vollenweider and Wareham, {Nicholas J} and Weir, {David R} and Whitfield, {John B} and Wilson, {James F} and Jessica Tyrrell and Frayling, {Timothy M} and In{\^e}s Barroso and Michael Boehnke and Panagiotis Deloukas and Fox, {Caroline S} and Hirschhorn, {Joel N} and Hunter, {David J} and Spector, {Tim D} and Strachan, {David P} and {van Duijn}, {Cornelia M} and Heid, {Iris M} and Mohlke, {Karen L} and Jonathan Marchini and Loos, {Ruth J F} and Kilpel{\"a}inen, {Tuomas O} and Ching-Ti Liu and Borecki, {Ingrid B} and North, {Kari E} and Cupples, {L Adrienne}",
note = "Acknowledgements A full list of acknowledgments appears in the Supplementary Note 4. Co-author A.J.M.d.C. recently passed away while this work was in process. This work was performed under the auspices of the Genetic Investigation of ANthropometric Traits (GIANT) consortium. We acknowledge the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium for encouraging CHARGE studies to participate in this effort and for the contributions of CHARGE members to the analyses conducted for this research. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (41071, 77299, 102318, 110413, 117787, 121584, 123885, 124243, 124282, 126925, 129378, 134309, 286284); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la 359 Recherche; Agency for Health Care Policy Research (HS06516); ALF/LUA research grant in Gothenburg; ALFEDIAM; ALK-Abell{\'o} A/S; Althingi; American Heart Association (13POST16500011); Amgen; Andrea and Charles Bronfman Philanthropies; Ardix Medical; Arthritis Research UK; Association Diab{\`e}te Risque Vasculaire; Australian National Health and Medical Research Council (241944, 339462, 389875, 389891, 389892, 389927, 389938, 442915, 442981, 496739, 552485, 552498); Avera Institute; Bayer Diagnostics; Becton Dickinson; BHF (RG/14/5/30893); Boston Obesity Nutrition Research Center (DK46200), Bristol-Myers Squibb; British Heart Foundation (RG/10/12/28456, RG2008/08, RG2008/014, SP/04/002); Medical Research Council of Canada; Canadian Institutes for Health Research (FRCN-CCT-83028); Cancer Research UK; Cardionics; Cavadis B.V., Center for Medical Systems Biology; Center of Excellence in Genomics; CFI; CIHR; City of Kuopio; CNAMTS; Cohortes Sant{\'e} TGIR; Contrat de Projets {\'E}tat-R{\'e}gion; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF-1333-00124, DFF-1331-00730B); County Council of Dalarna; Dalarna University; Danish Council for Strategic Research; Danish Diabetes Academy; Danish Medical Research Council; Department of Health, UK; Development Fund from the University of Tartu (SP1GVARENG); Diabetes Hilfs- und Forschungsfonds Deutschland; Diabetes UK; Diabetes Research and Wellness Foundation Fellowship; Donald W. Reynolds Foundation; Dr Robert Pfleger-Stiftung; Dutch Brain Foundation; Dutch Diabetes Research Foundation; Dutch Inter University Cardiology Institute; Dutch Kidney Foundation (E033); Dutch Ministry of Justice; the DynaHEALTH action No. 633595, Economic Structure Enhancing Fund of the Dutch Government; Else Kr{\"o}ner-Fresenius-Stiftung (2012_A147, P48/08//A11/08); Emil Aaltonen Foundation; Erasmus University Medical Center Rotterdam; Erasmus MC and Erasmus University Rotterdam; the Municipality of Rotterdam; Estonian Government (IUT20-60, IUT24-6); Estonian Research Roadmap through the Estonian Ministry of Education and Research (3.2.0304.11-0312); European Research Council (ERC Starting Grant and 323195:SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC); European Regional Development Fund; European Science Foundation (EU/QLRT-2001-01254); European Commission (018947, 018996, 201668, 223004, 230374, 279143, 284167, 305739, BBMRI-LPC-313010, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-2011-278913, HEALTH-2011-294713-EPLORE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2013-601456, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550-HYPERGENES, HEALTH-F7-305507 HOMAGE, IMI/115006, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2004-005272, LSHM-CT-2006-037697, LSHM-CT-2007-037273, QLG1-CT-2002-00896, QLG2-CT-2002-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ0103, 01ZZ0403, 01ZZ9603, 03IS2061A, 03ZIK012); Federal State of Mecklenburg-West Pomerania; F{\'e}d{\'e}ration Fran{\cc}aise de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Fondation Leducq; Food Standards Agency; Foundation for Strategic Research; French Ministry of Research; FRSQ; Genetic Association Information Network (GAIN) of the Foundation for the NIH; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); GlaxoSmithKline; Greek General Secretary of Research and Technology; G{\"o}teborg Medical Society; Health and Safety Executive; Healthcare NHS Trust; Healthway; Western Australia; Heart Foundation of Northern Sweden; Helmholtz Zentrum M{\"u}nchen—German Research Center for Environmental Health; Hjartavernd; Ingrid Thurings Foundation; INSERM; InterOmics (PB05 MIUR-CNR); INTERREG IV Oberrhein Program (A28); Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001); Italian Ministry of Health (ICS110.1/RF97.71); Italian Ministry of Economy and Finance (FaReBio di Qualit{\`a}); Marianne and Marcus Wallenberg Foundation; the Ministry of Health, Welfare and Sports, the Netherlands; J.D.E. and Catherine T, MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; KfH Stiftung Pr{\"a}ventivmedizin e.V.; King's College London; Knut and Alice Wallenberg Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); La Fondation de France; Leenaards Foundation; Lilly; LMUinnovativ; Lundberg Foundation; Magnus Bergvall Foundation; MDEIE; Medical Research Council UK (G0000934, G0601966, G0700931, MC_U106179471, MC_UU_12019/1); MEKOS Laboratories; Merck Sant{\'e}; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs of Mecklenburg-West Pomerania; Ministry of Economic Affairs, The Netherlands; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport in the Republic of Croatia (108-1080315-0302); MRC centre for Causal Analyses in Translational Epidemiology; MRC Human Genetics Unit; MRC-GlaxoSmithKline pilot programme (G0701863); MSD Stipend Diabetes; National Institute for Health Research; Netherlands Brain Foundation (F2013(1)-28); Netherlands CardioVascular Research Initiative (CVON2011-19); Netherlands Genomics Initiative (050-060-810); Netherlands Heart Foundation (2001 D 032, NHS2010B280); Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) (56-464-14192, 60-60600-97-118, 100-001-004, 261-98-710, 400-05-717, 480-04-004, 480-05-003, 481-08-013, 904-61-090, 904-61-193, 911-11-025, 985-10-002, Addiction-31160008, BBMRI–NL 184.021.007, GB-MaGW 452-04-314, GB-MaGW 452-06-004, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MW 940-38-011, Middelgroot-911-09-032, NBIC/BioAssist/RK 2008.024, Spinozapremie 175.010.2003.005, 175.010.2007.006); Neuroscience Campus Amsterdam; NHS Foundation Trust; National Institutes of Health (1RC2MH089951, 1Z01HG000024, 24152, 263MD9164, 263MD821336, 2R01LM010098, 32100-2, 32122, 32108, 5K99HL130580-02, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, AG13196, CA047988, DA12854, DK56350, DK063491, DK078150, DK091718, DK100383, DK078616, ES10126, HG004790, HHSN268200625226C, HHSN268200800007C, HHSN268201200036C, HHSN268201500001I, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, HL043851, HL45670, HL080467, HL085144, HL087660, HL054457, HL119443, HL118305, HL071981, HL034594, HL126024, HL130114, KL2TR001109, MH66206, MH081802, N01AG12100, N01HC55015, N01HC55016, N01C55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, N01HG65403, N01WH22110, N02HL6‐4278, N01-HC-25195, P01CA33619, R01HD057194, R01HD057194, R01AG023629, R01CA63, R01D004215701A, R01DK075787, R01DK062370, R01DK072193, R01DK075787, R01DK089256, R01HL53353, R01HL59367, R01HL086694, R01HL087641, R01HL087652, R01HL103612, R01HL105756, R01HL117078, R01HL120393, R03 AG046389, R37CA54281, RC2AG036495, RC4AG039029, RPPG040710371, RR20649, TW008288, TW05596, U01AG009740, U01CA98758, U01CA136792, U01DK062418, U01HG004402, U01HG004802, U01HG007376, U01HL080295, UL1RR025005, UL1TR000040, UL1TR000124, UL1TR001079, 2T32HL007055-36, T32GM074905, HG002651, HL084729, N01-HC-25195, UM1CA182913); NIH, National Institute on Aging (Intramural funding, NO1-AG-1-2109); Northern Netherlands Collaboration of Provinces; Novartis Pharma; Novo Nordisk; Novo Nordisk Foundation; Nutricia Research Foundation (2016-T1); ONIVINS; Parnassia Bavo group; Pierre Fabre; Province of Groningen; P{\"a}ivikki and Sakari Sohlberg Foundation; P{\aa}hlssons Foundation; Paavo Nurmi Foundation; Radboud Medical Center Nijmegen; Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Institute for Diseases in the Elderly; Research into Ageing; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Roche; Royal Society; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Government Health Directorates, Chief Scientist Office (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Soci{\'e}t{\'e} Francophone du 358 Diab{\`e}te; State of Bavaria; Stiftelsen f{\"o}r Gamla Tj{\"a}narinnor; Stockholm County Council (560183, 592229); Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Stroke Association; Swedish Diabetes Association; Swedish Diabetes Foundation (2013-024); Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20120197, 20150711); Swedish Research Council (0593, 8691, 2012-1397, 2012-1727, and 2012-2215); Swedish Society for Medical Research; Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 31003A-143914, 33CSCO-122661, 33CS30-139468, 33CS30-148401, 51RTP0_151019); Tampere Tuberculosis Foundation; Technology Foundation STW (11679); The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community (G.0880.13, G.0881.13); The Great Wine Estates of the Margaret River Region of Western Australia; Timber Merchant Vilhelm Bangs Foundation; Topcon; Tore Nilsson Foundation; Torsten and Ragnar S{\"o}derberg's Foundation; United States – Israel Binational Science Foundation (Grant 2011036), Ume{\aa} University; University Hospital of Regensburg; University of Groningen; University Medical Center Groningen; University of Michigan; University of Utrecht; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) (b2011036); Velux Foundation; VU University’s Institute for Health and Care Research; V{\"a}stra G{\"o}taland Foundation; Wellcome Trust (068545, 076113, 079895, 084723, 088869, WT064890, WT086596, WT098017, WT090532, WT098051, 098381); Wissenschaftsoffensive TMO; Yrj{\"o} Jahnsson Foundation; and {\AA}ke Wiberg Foundation. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute (NHLBI); the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services.",
year = "2017",
month = "4",
day = "26",
doi = "10.1038/ncomms14977",
language = "English",
volume = "8",
pages = "1--19",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

AU - Justice, Anne E

AU - Winkler, Thomas W

AU - Feitosa, Mary F

AU - Graff, Misa

AU - Fisher, Virginia A

AU - Young, Kristin

AU - Barata, Llilda

AU - Deng, Xuan

AU - Czajkowski, Jacek

AU - Hadley, David

AU - Ngwa, Julius S

AU - Ahluwalia, Tarunveer S

AU - Chu, Audrey Y

AU - Heard-Costa, Nancy L

AU - Lim, Elise

AU - Perez, Jeremiah

AU - Eicher, John D

AU - Kutalik, Zoltán

AU - Xue, Luting

AU - Mahajan, Anubha

AU - Renström, Frida

AU - Wu, Joseph

AU - Qi, Qibin

AU - Ahmad, Shafqat

AU - Alfred, Tamuno

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N1 - Acknowledgements A full list of acknowledgments appears in the Supplementary Note 4. Co-author A.J.M.d.C. recently passed away while this work was in process. This work was performed under the auspices of the Genetic Investigation of ANthropometric Traits (GIANT) consortium. We acknowledge the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium for encouraging CHARGE studies to participate in this effort and for the contributions of CHARGE members to the analyses conducted for this research. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (41071, 77299, 102318, 110413, 117787, 121584, 123885, 124243, 124282, 126925, 129378, 134309, 286284); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la 359 Recherche; Agency for Health Care Policy Research (HS06516); ALF/LUA research grant in Gothenburg; ALFEDIAM; ALK-Abelló A/S; Althingi; American Heart Association (13POST16500011); Amgen; Andrea and Charles Bronfman Philanthropies; Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; Australian National Health and Medical Research Council (241944, 339462, 389875, 389891, 389892, 389927, 389938, 442915, 442981, 496739, 552485, 552498); Avera Institute; Bayer Diagnostics; Becton Dickinson; BHF (RG/14/5/30893); Boston Obesity Nutrition Research Center (DK46200), Bristol-Myers Squibb; British Heart Foundation (RG/10/12/28456, RG2008/08, RG2008/014, SP/04/002); Medical Research Council of Canada; Canadian Institutes for Health Research (FRCN-CCT-83028); Cancer Research UK; Cardionics; Cavadis B.V., Center for Medical Systems Biology; Center of Excellence in Genomics; CFI; CIHR; City of Kuopio; CNAMTS; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF-1333-00124, DFF-1331-00730B); County Council of Dalarna; Dalarna University; Danish Council for Strategic Research; Danish Diabetes Academy; Danish Medical Research Council; Department of Health, UK; Development Fund from the University of Tartu (SP1GVARENG); Diabetes Hilfs- und Forschungsfonds Deutschland; Diabetes UK; Diabetes Research and Wellness Foundation Fellowship; Donald W. Reynolds Foundation; Dr Robert Pfleger-Stiftung; Dutch Brain Foundation; Dutch Diabetes Research Foundation; Dutch Inter University Cardiology Institute; Dutch Kidney Foundation (E033); Dutch Ministry of Justice; the DynaHEALTH action No. 633595, Economic Structure Enhancing Fund of the Dutch Government; Else Kröner-Fresenius-Stiftung (2012_A147, P48/08//A11/08); Emil Aaltonen Foundation; Erasmus University Medical Center Rotterdam; Erasmus MC and Erasmus University Rotterdam; the Municipality of Rotterdam; Estonian Government (IUT20-60, IUT24-6); Estonian Research Roadmap through the Estonian Ministry of Education and Research (3.2.0304.11-0312); European Research Council (ERC Starting Grant and 323195:SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC); European Regional Development Fund; European Science Foundation (EU/QLRT-2001-01254); European Commission (018947, 018996, 201668, 223004, 230374, 279143, 284167, 305739, BBMRI-LPC-313010, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-2011-278913, HEALTH-2011-294713-EPLORE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2013-601456, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550-HYPERGENES, HEALTH-F7-305507 HOMAGE, IMI/115006, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2004-005272, LSHM-CT-2006-037697, LSHM-CT-2007-037273, QLG1-CT-2002-00896, QLG2-CT-2002-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ0103, 01ZZ0403, 01ZZ9603, 03IS2061A, 03ZIK012); Federal State of Mecklenburg-West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Fondation Leducq; Food Standards Agency; Foundation for Strategic Research; French Ministry of Research; FRSQ; Genetic Association Information Network (GAIN) of the Foundation for the NIH; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); GlaxoSmithKline; Greek General Secretary of Research and Technology; Göteborg Medical Society; Health and Safety Executive; Healthcare NHS Trust; Healthway; Western Australia; Heart Foundation of Northern Sweden; Helmholtz Zentrum München—German Research Center for Environmental Health; Hjartavernd; Ingrid Thurings Foundation; INSERM; InterOmics (PB05 MIUR-CNR); INTERREG IV Oberrhein Program (A28); Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001); Italian Ministry of Health (ICS110.1/RF97.71); Italian Ministry of Economy and Finance (FaReBio di Qualità); Marianne and Marcus Wallenberg Foundation; the Ministry of Health, Welfare and Sports, the Netherlands; J.D.E. and Catherine T, MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; KfH Stiftung Präventivmedizin e.V.; King's College London; Knut and Alice Wallenberg Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); La Fondation de France; Leenaards Foundation; Lilly; LMUinnovativ; Lundberg Foundation; Magnus Bergvall Foundation; MDEIE; Medical Research Council UK (G0000934, G0601966, G0700931, MC_U106179471, MC_UU_12019/1); MEKOS Laboratories; Merck Santé; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs of Mecklenburg-West Pomerania; Ministry of Economic Affairs, The Netherlands; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport in the Republic of Croatia (108-1080315-0302); MRC centre for Causal Analyses in Translational Epidemiology; MRC Human Genetics Unit; MRC-GlaxoSmithKline pilot programme (G0701863); MSD Stipend Diabetes; National Institute for Health Research; Netherlands Brain Foundation (F2013(1)-28); Netherlands CardioVascular Research Initiative (CVON2011-19); Netherlands Genomics Initiative (050-060-810); Netherlands Heart Foundation (2001 D 032, NHS2010B280); Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) (56-464-14192, 60-60600-97-118, 100-001-004, 261-98-710, 400-05-717, 480-04-004, 480-05-003, 481-08-013, 904-61-090, 904-61-193, 911-11-025, 985-10-002, Addiction-31160008, BBMRI–NL 184.021.007, GB-MaGW 452-04-314, GB-MaGW 452-06-004, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MW 940-38-011, Middelgroot-911-09-032, NBIC/BioAssist/RK 2008.024, Spinozapremie 175.010.2003.005, 175.010.2007.006); Neuroscience Campus Amsterdam; NHS Foundation Trust; National Institutes of Health (1RC2MH089951, 1Z01HG000024, 24152, 263MD9164, 263MD821336, 2R01LM010098, 32100-2, 32122, 32108, 5K99HL130580-02, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, AG13196, CA047988, DA12854, DK56350, DK063491, DK078150, DK091718, DK100383, DK078616, ES10126, HG004790, HHSN268200625226C, HHSN268200800007C, HHSN268201200036C, HHSN268201500001I, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, HL043851, HL45670, HL080467, HL085144, HL087660, HL054457, HL119443, HL118305, HL071981, HL034594, HL126024, HL130114, KL2TR001109, MH66206, MH081802, N01AG12100, N01HC55015, N01HC55016, N01C55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, N01HG65403, N01WH22110, N02HL6‐4278, N01-HC-25195, P01CA33619, R01HD057194, R01HD057194, R01AG023629, R01CA63, R01D004215701A, R01DK075787, R01DK062370, R01DK072193, R01DK075787, R01DK089256, R01HL53353, R01HL59367, R01HL086694, R01HL087641, R01HL087652, R01HL103612, R01HL105756, R01HL117078, R01HL120393, R03 AG046389, R37CA54281, RC2AG036495, RC4AG039029, RPPG040710371, RR20649, TW008288, TW05596, U01AG009740, U01CA98758, U01CA136792, U01DK062418, U01HG004402, U01HG004802, U01HG007376, U01HL080295, UL1RR025005, UL1TR000040, UL1TR000124, UL1TR001079, 2T32HL007055-36, T32GM074905, HG002651, HL084729, N01-HC-25195, UM1CA182913); NIH, National Institute on Aging (Intramural funding, NO1-AG-1-2109); Northern Netherlands Collaboration of Provinces; Novartis Pharma; Novo Nordisk; Novo Nordisk Foundation; Nutricia Research Foundation (2016-T1); ONIVINS; Parnassia Bavo group; Pierre Fabre; Province of Groningen; Päivikki and Sakari Sohlberg Foundation; Påhlssons Foundation; Paavo Nurmi Foundation; Radboud Medical Center Nijmegen; Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Institute for Diseases in the Elderly; Research into Ageing; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Roche; Royal Society; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Government Health Directorates, Chief Scientist Office (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du 358 Diabète; State of Bavaria; Stiftelsen för Gamla Tjänarinnor; Stockholm County Council (560183, 592229); Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Stroke Association; Swedish Diabetes Association; Swedish Diabetes Foundation (2013-024); Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20120197, 20150711); Swedish Research Council (0593, 8691, 2012-1397, 2012-1727, and 2012-2215); Swedish Society for Medical Research; Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 31003A-143914, 33CSCO-122661, 33CS30-139468, 33CS30-148401, 51RTP0_151019); Tampere Tuberculosis Foundation; Technology Foundation STW (11679); The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community (G.0880.13, G.0881.13); The Great Wine Estates of the Margaret River Region of Western Australia; Timber Merchant Vilhelm Bangs Foundation; Topcon; Tore Nilsson Foundation; Torsten and Ragnar Söderberg's Foundation; United States – Israel Binational Science Foundation (Grant 2011036), Umeå University; University Hospital of Regensburg; University of Groningen; University Medical Center Groningen; University of Michigan; University of Utrecht; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) (b2011036); Velux Foundation; VU University’s Institute for Health and Care Research; Västra Götaland Foundation; Wellcome Trust (068545, 076113, 079895, 084723, 088869, WT064890, WT086596, WT098017, WT090532, WT098051, 098381); Wissenschaftsoffensive TMO; Yrjö Jahnsson Foundation; and Åke Wiberg Foundation. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute (NHLBI); the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services.

PY - 2017/4/26

Y1 - 2017/4/26

N2 - 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.

AB - 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.

KW - Journal Article

KW - Epidemiology

KW - genetics research

KW - genome-wide association studies

KW - obesity

U2 - 10.1038/ncomms14977

DO - 10.1038/ncomms14977

M3 - Article

VL - 8

SP - 1

EP - 19

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 14977

ER -