Genome-wide meta-analyses identify multiple loci associated with smoking behavior

H Furberg, Y. Kim, J Dackor, E Boerwinkle, N Franceschini, D Ardissino, L Bernardinelli, PM Mannucci, F Mauri, PA Merlini, D Absher, TL Assimes, SP Fortmann, C Iribarren, JW Knowles, T Quertermous, L Ferrucci, T Tanaka, JC Bis, CD FurbergT Haritunians, B McKnight, BM Psaty, KD Taylor, EL Thacker, P Almgren, L Groop, C Ladenvall, M Boehnke, AU Jackson, KL Mohlke, HM Stringham, J Tuomilehto, EJ Benjamin, SJ Hwang, D Levy, SR Preis, RS Vasan, J Duan, PV Gejman, DF Levinson, AR Sanders, JX Shi, EH Lips, JD Mckay, A Agudo, L Barzan, V Bencko, S Benhamou, X Castellsague, C Canova, DI Conway, E Fabianova, L Foretova, V Janout, CM Healy, I Holcatova, K Kjaerheim, P Lagiou, J Lissowska, R Lowry, TV Macfarlane, D Mates, L Richiardi, P Rudnai, N Szeszenia-Dabrowska, D Zaridze, A Znaor, M Lathrop, P Brennan, S Bandinelli, TM Frayling, JM Guralnik, Y Milaneschi, JRB Perry, D Altshuler, R Elosua, S Kathiresan, G Lucas, O Melander, CJ O'Donnell, V Salomaa, SM Schwartz, BF Voight, BW Penninx, JH Smit, N Vogelzangs, DI Boomsma, EJC de Geus, JM Vink, G Willemsen, SJ Chanock, FY Gu, SE Hankinson, DJ Hunter, Bert Hofman, Henning Tiemeier, André Uitterlinden, Cornelia Duijn, Stefan Walter, DI Chasman, BM Everett, G Pare, PM Ridker, MD Li, HH Maes, J Audrain-McGovern, D Posthuma, LM Thornton, C Lerman, J Kaprio, JE Rose, JPA Ioannidis, P Kraft, DY Lin, PF Sullivan

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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.
Original languageUndefined/Unknown
Pages (from-to)441-U134
JournalNature Genetics
Volume42
Issue number5
DOIs
Publication statusPublished - 2010

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