Authors:
Helena Furberg, YunJung Kim, Jennifer Dackor, Eric Boerwinkle, Nora Franceschini, Diego Ardissino, Luisa Bernardinelli, Pier M Mannucci, Francesco Mauri, Piera A Merlini, Devin Absher, Themistocles L Assimes, Stephen P Fortmann, Carlos Iribarren, Joshua W Knowles, Thomas Quertermous, Luigi Ferrucci, Toshiko Tanaka, Joshua C Bis, Curt D Furberg, Talin Haritunians, Barbara McKnight, Bruce M Psaty, Kent D Taylor, Evan L Thacker, Peter Almgren, Leif Groop, Claes Ladenvall, Michael Boehnke, Anne U Jackson, Karen L Mohlke, Heather M Stringham, Jaakko Tuomilehto, Emelia J Benjamin, Shih-Jen Hwang, Daniel Levy, Sarah Rosner Preis, Ramachandran S Vasan, Jubao Duan, Pablo V Gejman, Douglas F Levinson, Alan R Sanders, Jianxin Shi, Esther H Lips, James D McKay, Antonio Agudo, Luigi Barzan, Vladimir Bencko, Simone Benhamou, Xavier Castellsagué, Cristina Canova, David I Conway, Eleonora Fabianova, Lenka Foretova, Vladimir Janout, Claire M Healy, Ivana Holcátová, Kristina Kjaerheim, Pagona Lagiou, Jolanta Lissowska, Ray Lowry, Tatiana V Macfarlane, Dana Mates, Lorenzo Richiardi, Peter Rudnai, Neonilia Szeszenia-Dabrowska, David Zaridze, Ariana Znaor, Mark Lathrop, Paul Brennan, Stefania Bandinelli, Timothy M Frayling, Jack M Guralnik, Yuri Milaneschi, John R B Perry, David Altshuler, Roberto Elosua, Sek Kathiresan, Gavin Lucas, Olle Melander, Christopher J O'Donnell, Veikko Salomaa, Stephen M Schwartz, Benjamin F Voight, Brenda W Penninx, Johannes H Smit, Nicole Vogelzangs, Dorret I Boomsma, Eco J C de Geus, Jacqueline M Vink, Gonneke Willemsen, Stephen J Chanock, Fangyi Gu, Susan E Hankinson, David J Hunter, Albert Hofman, Henning Tiemeier, Andre G Uitterlinden, Cornelia M van Duijn, Stefan Walter, Daniel I Chasman, Brendan M Everett, Guillaume Paré, Paul M Ridker, Ming D Li, Hermine H Maes, Janet Audrain-McGovern, Danielle Posthuma, Laura M Thornton, Caryn Lerman, Jaakko Kaprio, Jed E Rose, John P A Ioannidis, Peter Kraft, Dan-Yu Lin, & Patrick F Sullivan
Summary:
Consistent but indirect evidence has implicated genetic factors in smoking behavior. 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], β = 1.03, standard error (s.e.) = 0.053, P = 2.8 × 10−73). Two 10q25 SNPs (rs1329650[G], β = 0.367, s.e. = 0.059, P = 5.7 × 10−10; and rs1028936[A], β = 0.446, s.e. = 0.074, P = 1.3 × 10−9) and one 9q13 SNP in EGLN2 (rs3733829[G], β = 0.333, s.e. = 0.058, P = 1.0 × 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 × 10−8). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08–1.18, P = 3.6 × 10−8) was significantly associated with smoking cessation.
Source:
Nature Genetics; 42, 441-447 (04/25/10)