| 5. | Nat Genet. 2010 May;42(5):441-7. Epub 2010 Apr 25.Tobacco and Genetics Consortium. Collaborators: Furberg H, Kim Y, Dackor J, Boerwinkle E, Franceschini N, Ardissino D, Bernardinelli L, Mannucci PL, Mauri F, Merlini PA, Absher D, Assimes TL, Fortmann SP, Iribarren C, Knowles JW, Quertermous T, Ferrucci L, Tanaka T, Bis JC, Furberg CD, Haritunians T, McKnight B, Psaty BM, Taylor KD, Thacker EL, Almgren P, Groop L, Ladenvall C, Boehnke M, Jackson AU, Mohlke KL, Stringham HM, Tuomilehto J, Benjamin EJ, Hwang SJ, Levy D, Preis SR, Vasan RS, Duan J, Gejman PV, Levinson DF, Sanders AR, Shi J, Lips EH, McKay JD, Agudo A, Barzan L, Bencko V, Benhamou S, Castellsague X, Canova C, Conway DI, Fabianova E, Foretova L, Janout V, Healy CM, Holcátová I, Kjaerheim K, Lagiou P, Lissowska J, Lowry R, Macfarlane TV, Mates D, Richiardi L, Rudnai P, Szeszenia-Dabrowska N, Zaridze D, Znaor A, Lathrop M, Brennan P, Bandinelli S, Frayling TM, Guralnik JM, Milaneschi Y, Perry JR, Altshuler D, Elosua R, Kathiresan S, Lucas G, Melander O, O'Donnell CJ, Salomaa V, Schwartz SM, Voight BF, Penninx BW, Smit JH, Vogelzangs N, Boomsma DI, de Geus EJ, Vink JM, Willemsen G, Chanock SJ, Gu F, Hankinson SE, Hunter DJ, Hofman A, Tiemeier H, Uitterlinden AG, van Duijn CM, Walter S, Chasman DI, Everett BM, Paré G, Ridker PM, Li MD, Maes HH, Audrain-McGovern J, Posthuma D, Thornton LM, Lerman C, Kaprio J, Rose JE, Ioannidis JP, Kraft P, Lin DY, Sullivan PF. Department of Genetics, University of North Carolina, Chapel Hill, NC 27710, USA. Comment in: AbstractConsistent 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], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 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. |
