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 L Young; Llilda Barata; Xuan Deng; Jacek Czajkowski; David Hadley; Julius S Ngwa; Tarunveer Singh Ahluwalia; Audrey Y Chu; Nancy L Heard-Costa; Elise Lim; Jeremiah Perez; John D Eicher; Zoltan Kutalik; Luting Xue; Anubha Mahajan; Frida Renström; Joseph C Wu; Qibin Qi; Shafqat Ahmad; Tamuno Alfred; Najaf Amin; Lawrence F Bielak; Amélie Bonnefond; Jennifer L Bragg-Gresham; Gemma Cadby; Martina Chittani; Scott Coggeshall; Tanguy Corre; Nese Direk; Joel Eriksson; Krista Fischer; Mathias Gorski; Marie Neergaard Harder; Momoko Horikoshi; Tao-wei 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; Goncalo 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 P Bottinger; Daniele Braga; Brendan M Buckley; Steve Buyske; Harry Campbell; John C Chambers; Francis S Collins; Joanne E Curran; Gert Jan 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 A 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; Stéphane 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; Dabeeru C Rao; Laura J Rasmussen-Torvik; Rajesh Rawal; Treva K 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; Gerard 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; Cornélia M van Duijn; Iris M Heid; Karen L Mohlke; Jonathan L Marchini; Ruth J F Loos; Tuomas O Kilpeläinen; Ching-Ti Liu; Ingrid B Borecki; Kari E North; L Adrienne Cupples

doi:10.1038/ncomms14977

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 L Young, Llilda Barata, Xuan Deng, Jacek Czajkowski, David Hadley, Julius S Ngwa, Tarunveer Singh Ahluwalia, Audrey Y Chu, Nancy L Heard-Costa, Elise Lim, Jeremiah Perez, John D Eicher, Zoltan Kutalik, Luting Xue, Anubha MahajanFrida Renström, Joseph C Wu, Qibin Qi, Shafqat Ahmad, Tamuno Alfred, Najaf Amin, Lawrence F Bielak, Amélie Bonnefond, Jennifer L Bragg-Gresham, Gemma Cadby, Martina Chittani, Scott Coggeshall, Tanguy Corre, Nese Direk, Joel Eriksson, Krista Fischer, Mathias Gorski, Marie Neergaard Harder, Momoko Horikoshi, Tao-wei 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, Goncalo 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 P Bottinger, Daniele Braga, Brendan M Buckley, Steve Buyske, Harry Campbell, John C Chambers, Francis S Collins, Joanne E Curran, Gert Jan 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 A 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, Stéphane 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, Dabeeru C Rao, Laura J Rasmussen-Torvik, Rajesh Rawal, Treva K 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, Gerard 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, Cornélia M van Duijn, Iris M Heid, Karen L Mohlke, Jonathan L Marchini, Ruth J F Loos, Tuomas O Kilpeläinen, Ching-Ti Liu, Ingrid B Borecki, Kari E North, L Adrienne Cupples

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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 language	English
Article number	14977
Journal	Nature Communications
Volume	8
Number of pages	19
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms14977
Publication status	Published - 26 Apr 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Justice, A. E., Winkler, T. W., Feitosa, M. F., Graff, M., Fisher, V. A., Young, K. L., Barata, L., Deng, X., Czajkowski, J., Hadley, D., Ngwa, J. S., Ahluwalia, T. S., Chu, A. Y., Heard-Costa, N. L., Lim, E., Perez, J., Eicher, J. D., Kutalik, Z., Xue, L., ... 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, Article 14977. https://doi.org/10.1038/ncomms14977

Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, VA, Young, KL, 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, JC, Qi, Q, Ahmad, S, Alfred, T, Amin, N, Bielak, LF, Bonnefond, A, Bragg-Gresham, JL, 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, EP, 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, LA, 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, MR, 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, TK, 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, HJ, 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, JL, 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. https://doi.org/10.1038/ncomms14977

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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",

author = "Justice, {Anne E} and Winkler, {Thomas W} and Feitosa, {Mary F} and Misa Graff and Fisher, {Virginia A} and Young, {Kristin L} and Llilda Barata and Xuan Deng and Jacek Czajkowski and David Hadley and Ngwa, {Julius S} and Ahluwalia, {Tarunveer Singh} and Chu, {Audrey Y} and Heard-Costa, {Nancy L} and Elise Lim and Jeremiah Perez and Eicher, {John D} and Zoltan Kutalik and Luting Xue and Anubha Mahajan and Frida Renstr{\"o}m and Wu, {Joseph C} and Qibin Qi and Shafqat Ahmad and Tamuno Alfred and Najaf Amin and Bielak, {Lawrence F} and Am{\'e}lie Bonnefond and Bragg-Gresham, {Jennifer L} 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-wei 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 Stan{\v c}{\'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, {Goncalo 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 Bottinger, {Erwin P} 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 Jan} 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 Hindorff, {Lucia A} 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 Jarvelin, {Marjo Riitta} 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 St{\'e}phane 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, {Dabeeru C} and Rasmussen-Torvik, {Laura J} and Rajesh Rawal and Rice, {Treva K} 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 Gerard 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 Grabe, {Hans J{\"o}rgen} 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}, {Corn{\'e}lia M} and Heid, {Iris M} and Mohlke, {Karen L} and Marchini, {Jonathan L} 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}",

year = "2017",

month = apr,

day = "26",

doi = "10.1038/ncomms14977",

language = "English",

volume = "8",

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 L

AU - Barata, Llilda

AU - Deng, Xuan

AU - Czajkowski, Jacek

AU - Hadley, David

AU - Ngwa, Julius S

AU - Ahluwalia, Tarunveer Singh

AU - Chu, Audrey Y

AU - Heard-Costa, Nancy L

AU - Lim, Elise

AU - Perez, Jeremiah

AU - Eicher, John D

AU - Kutalik, Zoltan

AU - Xue, Luting

AU - Mahajan, Anubha

AU - Renström, Frida

AU - Wu, Joseph C

AU - Qi, Qibin

AU - Ahmad, Shafqat

AU - Alfred, Tamuno

AU - Amin, Najaf

AU - Bielak, Lawrence F

AU - Bonnefond, Amélie

AU - Bragg-Gresham, Jennifer L

AU - Cadby, Gemma

AU - Chittani, Martina

AU - Coggeshall, Scott

AU - Corre, Tanguy

AU - Direk, Nese

AU - Eriksson, Joel

AU - Fischer, Krista

AU - Gorski, Mathias

AU - Neergaard Harder, Marie

AU - Horikoshi, Momoko

AU - Huang, Tao-wei

AU - Huffman, Jennifer E

AU - Jackson, Anne U

AU - Justesen, Johanne Marie

AU - Kanoni, Stavroula

AU - Kinnunen, Leena

AU - Kleber, Marcus E

AU - Komulainen, Pirjo

AU - Kumari, Meena

AU - Lim, Unhee

AU - Luan, Jian'an

AU - Lyytikäinen, Leo-Pekka

AU - Mangino, Massimo

AU - Manichaikul, Ani

AU - Marten, Jonathan

AU - Middelberg, Rita P S

AU - Müller-Nurasyid, Martina

AU - Navarro, Pau

AU - Pérusse, Louis

AU - Pervjakova, Natalia

AU - Sarti, Cinzia

AU - Smith, Albert Vernon

AU - Smith, Jennifer A

AU - Stančáková, Alena

AU - Strawbridge, Rona J

AU - Stringham, Heather M

AU - Sung, Yun Ju

AU - Tanaka, Toshiko

AU - Teumer, Alexander

AU - Trompet, Stella

AU - van der Laan, Sander W

AU - van der Most, Peter J

AU - van Vliet-Ostaptchouk, Jana V

AU - Vedantam, Sailaja L

AU - Verweij, Niek

AU - Vink, Jacqueline M

AU - Vitart, Veronique

AU - Wu, Ying

AU - Yengo, Loic

AU - Zhang, Weihua

AU - Hua Zhao, Jing

AU - Zimmermann, Martina E

AU - Zubair, Niha

AU - Abecasis, Goncalo R

AU - Adair, Linda S

AU - Afaq, Saima

AU - Afzal, Uzma

AU - Bakker, Stephan J L

AU - Bartz, Traci M

AU - Beilby, John

AU - Bergman, Richard N

AU - Bergmann, Sven

AU - Biffar, Reiner

AU - Blangero, John

AU - Boerwinkle, Eric

AU - Bonnycastle, Lori L

AU - Bottinger, Erwin P

AU - Braga, Daniele

AU - Buckley, Brendan M

AU - Buyske, Steve

AU - Campbell, Harry

AU - Chambers, John C

AU - Collins, Francis S

AU - Curran, Joanne E

AU - de Borst, Gert Jan

AU - De Craen, Anton J M

AU - de Geus, Eco J C

AU - Dedoussis, George

AU - Delgado, Graciela E

AU - den Ruijter, Hester M

AU - Eiriksdottir, Gudny

AU - Eriksson, Anna L

AU - Esko, Tõnu

AU - Faul, Jessica D

AU - Ford, Ian

AU - Forrester, Terrence

AU - Gertow, Karl

AU - Gigante, Bruna

AU - Glorioso, Nicola

AU - Gong, Jian

AU - Grallert, Harald

AU - Grammer, Tanja B

AU - Grarup, Niels

AU - Haitjema, Saskia

AU - Hallmans, Göran

AU - Hamsten, Anders

AU - Hansen, Torben

AU - Harris, Tamara B

AU - Hartman, Catharina A

AU - Hassinen, Maija

AU - Hastie, Nicholas D

AU - Heath, Andrew C

AU - Hernandez, Dena

AU - Hindorff, Lucia A

AU - Hocking, Lynne J

AU - Hollensted, Mette

AU - Holmen, Oddgeir L

AU - Homuth, Georg

AU - Jan Hottenga, Jouke

AU - Huang, Jie

AU - Hung, Joseph

AU - Hutri-Kähönen, Nina

AU - Ingelsson, Erik

AU - James, Alan L

AU - Jansson, John-Olov

AU - Jarvelin, Marjo Riitta

AU - Jhun, Min A

AU - Jørgensen, Marit E

AU - Juonala, Markus

AU - Kähönen, Mika

AU - Karlsson, Magnus

AU - Koistinen, Heikki A

AU - Kolcic, Ivana

AU - Kolovou, Genovefa

AU - Kooperberg, Charles

AU - Krämer, Bernhard K

AU - Kuusisto, Johanna

AU - Kvaløy, Kirsti

AU - Lakka, Timo A

AU - Langenberg, Claudia

AU - Launer, Lenore J

AU - Leander, Karin

AU - Lee, Nanette R

AU - Lind, Lars

AU - Lindgren, Cecilia M

AU - Linneberg, Allan

AU - Lobbens, Stéphane

AU - Loh, Marie

AU - Lorentzon, Mattias

AU - Luben, Robert

AU - Lubke, Gitta

AU - Ludolph-Donislawski, Anja

AU - Lupoli, Sara

AU - Madden, Pamela A F

AU - Männikkö, Reija

AU - Marques-Vidal, Pedro

AU - Martin, Nicholas G.

AU - Mckenzie, Colin A

AU - McKnight, Barbara

AU - Mellström, Dan

AU - Menni, Cristina

AU - Montgomery, Grant W.

AU - Musk, Aw Bill

AU - Narisu, Narisu

AU - Nauck, Matthias

AU - Nolte, Ilja M

AU - Oldehinkel, Albertine J

AU - Olden, Matthias

AU - Ong, Ken K

AU - Padmanabhan, Sandosh

AU - Peyser, Patricia A

AU - Pisinger, Charlotta

AU - Porteous, David J

AU - Raitakari, Olli T

AU - Rankinen, Tuomo

AU - Rao, Dabeeru C

AU - Rasmussen-Torvik, Laura J

AU - Rawal, Rajesh

AU - Rice, Treva K

AU - Ridker, Paul M

AU - Rose, Lynda M

AU - Bien, Stephanie A

AU - Rudan, Igor

AU - Sanna, Serena

AU - Sarzynski, Mark A

AU - Sattar, Naveed

AU - Savonen, Kai

AU - Schlessinger, David

AU - Scholtens, Salome

AU - Schurmann, Claudia

AU - Scott, Robert A

AU - Sennblad, Bengt

AU - Siemelink, Marten A

AU - Silbernagel, Günther

AU - Slagboom, P Eline

AU - Snieder, Harold

AU - Staessen, Jan A.

AU - Stott, David J

AU - Swertz, Morris A

AU - Swift, Amy J

AU - Taylor, Kent D

AU - Tayo, Bamidele O

AU - Thorand, Barbara

AU - Thuillier, Dorothee

AU - Tuomilehto, Jaakko

AU - Uitterlinden, Andre G

AU - Vandenput, Liesbeth

AU - Vohl, Marie-Claude

AU - Völzke, Henry

AU - Vonk, Judith M

AU - Waeber, Gerard

AU - Waldenberger, Melanie

AU - Westendorp, R G J

AU - Wild, Sarah

AU - Willemsen, Gonneke

AU - Wolffenbuttel, Bruce H R

AU - Wong, Andrew

AU - Wright, Alan F

AU - Zhao, Wei

AU - Zillikens, M Carola

AU - Baldassarre, Damiano

AU - Balkau, Beverley

AU - Bandinelli, Stefania

AU - Böger, Carsten A

AU - Boomsma, Dorret I

AU - Bouchard, Claude

AU - Bruinenberg, Marcel

AU - Chasman, Daniel I

AU - Chen, Yii-DerIda

AU - Chines, Peter S

AU - Cooper, Richard S

AU - Cucca, Francesco

AU - Cusi, Daniele

AU - Faire, Ulf de

AU - Ferrucci, Luigi

AU - Franks, Paul W

AU - Froguel, Philippe

AU - Gordon-Larsen, Penny

AU - Grabe, Hans Jörgen

AU - Gudnason, Vilmundur

AU - Haiman, Christopher A

AU - Hayward, Caroline

AU - Hveem, Kristian

AU - Johnson, Andrew D

AU - Wouter Jukema, J

AU - Kardia, Sharon L R

AU - Kivimaki, Mika

AU - Kooner, Jaspal S

AU - Kuh, Diana

AU - Laakso, Markku

AU - Lehtimäki, Terho

AU - Marchand, Loic Le

AU - März, Winfried

AU - McCarthy, Mark I

AU - Metspalu, Andres

AU - Morris, Andrew P

AU - Ohlsson, Claes

AU - Palmer, Lyle J

AU - Pasterkamp, Gerard

AU - Pedersen, Oluf

AU - Peters, Annette

AU - Peters, Ulrike

AU - Polasek, Ozren

AU - Psaty, Bruce M

AU - Qi, Lu

AU - Rauramaa, Rainer

AU - Smith, Blair H

AU - Sørensen, Thorkild I A

AU - Strauch, Konstantin

AU - Tiemeier, Henning

AU - Tremoli, Elena

AU - van der Harst, Pim

AU - Vestergaard, Henrik

AU - Vollenweider, Peter

AU - Wareham, Nicholas J

AU - Weir, David R

AU - Whitfield, John B

AU - Wilson, James F

AU - Tyrrell, Jessica

AU - Frayling, Timothy M

AU - Barroso, Inês

AU - Boehnke, Michael

AU - Deloukas, Panagiotis

AU - Fox, Caroline S

AU - Hirschhorn, Joel N

AU - Hunter, David J

AU - Spector, Tim D

AU - Strachan, David P

AU - van Duijn, Cornélia M

AU - Heid, Iris M

AU - Mohlke, Karen L

AU - Marchini, Jonathan L

AU - Loos, Ruth J F

AU - Kilpeläinen, Tuomas O

AU - Liu, Ching-Ti

AU - Borecki, Ingrid B

AU - North, Kari E

AU - Cupples, L Adrienne

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

U2 - 10.1038/ncomms14977

DO - 10.1038/ncomms14977

M3 - Journal article

C2 - 28443625

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 14977

ER -

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

Abstract

Keywords

UN SDGs

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