151. Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- Author
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Furberg, Helena Kim, YunJung Dackor, Jennifer Boerwinkle, Eric Franceschini, Nora Ardissino, Diego Bernardinelli, Luisa Mannucci, Pier M. Mauri, Francesco Merlini, Piera A. and Absher, Devin Assimes, Themistocles L. Fortmann, Stephen P. and Iribarren, Carlos Knowles, Joshua W. Quertermous, Thomas and Ferrucci, Luigi Tanaka, Toshiko Bis, Joshua C. Furberg, Curt D. Haritunians, Talin McKnight, Barbara Psaty, Bruce M. and Taylor, Kent D. Thacker, Evan L. Almgren, Peter Groop, Leif and Ladenvall, Claes Boehnke, Michael Jackson, Anne U. and Mohlke, Karen L. Stringham, Heather M. Tuomilehto, Jaakko and Benjamin, Emelia J. Hwang, Shih-Jen Levy, Daniel Preis, Sarah Rosner Vasan, Ramachandran S. Duan, Jubao Gejman, Pablo V. Levinson, Douglas F. Sanders, Alan R. Shi, Jianxin and Lips, Esther H. Mckay, James D. Agudo, Antonio Barzan, Luigi Bencko, Vladimir Benhamou, Simone Castellsague, Xavier and Canova, Cristina Conway, David I. Fabianova, Eleonora and Foretova, Lenka Janout, Vladimir Healy, Claire M. Holcatova, Ivana Kjaerheim, Kristina Lagiou, Pagona Lissowska, Jolanta and Lowry, Ray Macfarlane, Tatiana V. Mates, Dana Richiardi, Lorenzo Rudnai, Peter Szeszenia-Dabrowska, Neonilia Zaridze, David Znaor, Ariana Lathrop, Mark Brennan, Paul and Bandinelli, Stefania Frayling, Timothy M. Guralnik, Jack M. and Milaneschi, Yuri Perry, John R. B. Altshuler, David Elosua, Roberto Kathiresan, Sek Lucas, Gavin Melander, Olle and O'Donnell, Christopher J. Salomaa, Veikko Schwartz, Stephen M. and Voight, Benjamin F. Penninx, Brenda W. Smit, Johannes H. and Vogelzangs, Nicole Boomsma, Dorret I. de Geus, Eco J. C. and Vink, Jacqueline M. Willemsen, Gonneke Chanock, Stephen J. and Gu, Fangyi Hankinson, Susan E. Hunter, David J. Hofman, Albert Tiemeier, Henning Uitterlinden, Andre G. van Duijn, Cornelia M. Walter, Stefan Chasman, Daniel I. Everett, Brendan M. Pare, Guillaume Ridker, Paul M. Li, Ming D. and Maes, Hermine H. Audrain-McGovern, Janet Posthuma, Danielle and Thornton, Laura M. Lerman, Caryn Kaprio, Jaakko Rose, Jed E. and Ioannidis, John P. A. Kraft, Peter Lin, Dan-Yu Sullivan, Patrick F.
- Abstract
Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
- Published
- 2010