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, Zoltan; Xue, Luting; Mahajan, Anubha; Renstrom, 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; Harder, Marie Neergaard; 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.; Mueller-Nurasyid, Martina; Navarro, Pau; Perusse, Louis; Pervjakova, Natalia; Sarti, Cinzia; Smith, Albert Vernon; Smith, Jennifer A.; Stancakova, 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; Zhao, Jing Hua; Zimmermann, Martina E.; Zubair, Niha; Abecasis, Goncalo 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, Tonu; 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, Goran; 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; Hottenga, Jouke Jan; Huang, Jie; Hung, Joseph; Hutri-Kähönen, Nina; Ingelsson, Erik; James, Alan L.; Jansson, John-Olov; Järvelin, Marjo-Riitta; Jhun, Min A.; Jorgensen, Marit E.; Juonala, Markus; Kähönen, Mika; Karlsson, Magnus; Koistinen, Heikki A.; Kolcic, Ivana; Kolovou, Genovefa; Kooperberg, Charles; Kramer, Bernhard K.; Kuusisto, Johanna; Kvaloy, 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; Mellstrom, Dan; Menni, Cristina; Montgomery, Grant W.; Musk, A. W. (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, Gunther; 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; Volzke, Henry; Vonk, Judith M.; Waeber, Gerard; 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; Boger, Carsten A.; Boomsma, Dorret I.; Bouchard, Claude; Bruinenberg, Marcel; Chasman, Daniel I.; Chen, Yii-Der Ida; Chines, Peter S.; Cooper, Richard S.; Cucca, Francesco; Cusi, Daniele; de Faire, Ulf; Ferrucci, Luigi; Franks, Paul W.; Froguel, Philippe; Gordon-Larsen, Penny; Grabe, Hans-Jorgen; Gudnason, Vilmundur; Haiman, Christopher A.; Hayward, Caroline; Hveem, Kristian; Johnson, Andrew D.; Jukema, Wouter; Kardia, Sharon L. R.; Kivimäki, Mika; Kooner, Jaspal S.; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Le Marchand, Loic; Marz, 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.; Sorensen, 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, Ines; 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 (2017-04-26)
 
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URL:
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, Zoltan
Xue, Luting
Mahajan, Anubha
Renstrom, 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
Harder, Marie Neergaard
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.
Mueller-Nurasyid, Martina
Navarro, Pau
Perusse, Louis
Pervjakova, Natalia
Sarti, Cinzia
Smith, Albert Vernon
Smith, Jennifer A.
Stancakova, 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
Zhao, Jing Hua
Zimmermann, Martina E.
Zubair, Niha
Abecasis, Goncalo 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, Tonu
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, Goran
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
Hottenga, Jouke Jan
Huang, Jie
Hung, Joseph
Hutri-Kähönen, Nina
Ingelsson, Erik
James, Alan L.
Jansson, John-Olov
Järvelin, Marjo-Riitta
Jhun, Min A.
Jorgensen, Marit E.
Juonala, Markus
Kähönen, Mika
Karlsson, Magnus
Koistinen, Heikki A.
Kolcic, Ivana
Kolovou, Genovefa
Kooperberg, Charles
Kramer, Bernhard K.
Kuusisto, Johanna
Kvaloy, 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
Mellstrom, Dan
Menni, Cristina
Montgomery, Grant W.
Musk, A. W. (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, Gunther
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
Volzke, Henry
Vonk, Judith M.
Waeber, Gerard
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
Boger, Carsten A.
Boomsma, Dorret I.
Bouchard, Claude
Bruinenberg, Marcel
Chasman, Daniel I.
Chen, Yii-Der Ida
Chines, Peter S.
Cooper, Richard S.
Cucca, Francesco
Cusi, Daniele
de Faire, Ulf
Ferrucci, Luigi
Franks, Paul W.
Froguel, Philippe
Gordon-Larsen, Penny
Grabe, Hans-Jorgen
Gudnason, Vilmundur
Haiman, Christopher A.
Hayward, Caroline
Hveem, Kristian
Johnson, Andrew D.
Jukema, Wouter
Kardia, Sharon L. R.
Kivimäki, Mika
Kooner, Jaspal S.
Kuh, Diana
Laakso, Markku
Lehtimäki, Terho
Le Marchand, Loic
Marz, 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.
Sorensen, 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, Ines
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
Springer Nature
26.04.2017

Justice, A. E. et al. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat. Commun. 8, 14977 doi: 10.1038/ncomms14977 (2017)

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doi:https://doi.org/10.1038/ncomms14977
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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.

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