Genome-Wide Meta-Analysis of 241,258 Adults Accounting for Smoking Behaviour Identifies Novel Loci for Obesity Traits

Citation

Justice, Anne E.; Winkler, Thomas W.; Feitosa, Mary F.; Graff, Mariaelisa; Fisher, Virginia A.; Young, Kristin L.; Barata, Llilda P.; Deng, Xuan; Czajkowski, Jacek; & Hadley, David, et al. (2017). Genome-Wide Meta-Analysis of 241,258 Adults Accounting for Smoking Behaviour Identifies Novel Loci for Obesity Traits. Nature Communications, 8, 14977. PMCID: PMC5414044

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.

URL

http://dx.doi.org/10.1038/ncomms14977

Reference Type

Journal Article

Year Published

2017

Journal Title

Nature Communications

Author(s)

Justice, Anne E.
Winkler, Thomas W.
Feitosa, Mary F.
Graff, Mariaelisa
Fisher, Virginia A.
Young, Kristin L.
Barata, Llilda P.
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
Renström, Frida
Wu, Joseph
Qi, Qibin
Ahmad, Shafqat
Alfred, Tamuno
Amin, Najaf
Bielak, Lawrence F.
Bonnefond, Amelie
Bragg-Gresham, Jennifer L.
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 M.
Kanoni, Stavroula
Kinnunen, Leena
Kleber, Marcus E.
Komulainen, Pirjo
Kumari, Meena
Lim, Unhee
Luan, Jian'an
Lyytikainen, Leo-Pekka
Mangino, Massimo
Manichaikul, Ani
Marten, Jonathan
Middelberg, Rita P. S.
Muller-Nurasyid, Martina
Navarro, Pau
Perusse, Louis
Pervjakova, Natalia
Sarti, Cinzia
Smith, Albert V.
Smith, Jennifer A.
Stancakova, Alena
Strawbridge, Rona J.
Stringham, Heather M.
Sung, Yun J.
Tanaka, Toshiko
Teumer, Alexander
Trompet, Stella
van der Laan, Sander W.
van der Most, Peter J.
Van Vliet-Ostaptchouk, Jana V.
Vedantam, Sailaja
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 A.
Bonnycastle, Lori L.
Bottinger, Erwin P.
Braga, Daniele
Buckley, Brendan M.
Buyske, Steven G.
Campbell, Harry
Chambers, John C.
Collins, Francis S.
Curran, Joanne E.
de Borst, Gert J.
de Craen, Antonius 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 A.
Hocking, Lynne J.
Hollensted, Mette
Holmen, Oddgeir L.
Homuth, Georg
Jan Hottenga, Jouke
Huang, Jie
Hung, Joseph
Hutri-Kahonen, Nina
Ingelsson, Erik
James, Alan L.
Jansson, John-Olov
Jarvelin, Marjo-Riitta
Jhun, Min A.
Jorgensen, Marit E.
Juonala, Markus
Kahonen, Mika
Karlsson, Magnus
Koistinen, Heikki A.
Kolcic, Ivana
Kolovou, Genovefa
Kooperberg, Charles L.
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.
Mannikko, Reija
Marques-Vidal, Pedro
Martin, Nicholas G.
McKenzie, Colin A.
McKnight, Barbara
Mellstrom, Dan
Menni, Cristina
Montgomery, Grant W.
Musk, Arthur W.
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, Dabeeru C.
Rasmussen-Torvik, Laura J.
Rawal, Rajesh
Rice, Treva K.
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, Rudi G. J.
Wild, Sarah H.
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 G.
Haiman, Christopher A.
Hayward, Caroline
Hveem, Kristian
Johnson, Andrew D.
Wouter Jukema, J.
Kardia, Sharon L. R.
Kivimaki, Mika
Kooner, Jaspal Singh S.
Kuh, Diana
Laakso, Markku
Lehtimaki, 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, Timothy D.
Strachan, David P.
van Duijn, Cornelia M.
Heid, Iris M.
Mohlke, Karen L.
Marchini, Jonathan
Loos, Ruth J. F.
Kilpelainen, Tuomas O.
Liu, Ching-Ti
Borecki, Ingrid B.
North, Kari E.
Cupples, L. Adrienne

PMCID

PMC5414044

ORCiD

Gordon-Larsen - 0000-0001-5322-4188
Adair - 0000-0002-3670-8073
Graff - 0000-0001-6380-1735