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

Lookup NU author(s): Dr Ray Lowry


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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.

Publication metadata

Author(s): Furberg H, Kim Y, Dackor J, Boerwinkle E, Franceschini N, Ardissino D, Bernardinelli L, Mannucci PM, 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 JX, 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, Holcatova 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 JRB, 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 EJC, Vink JM, Willemsen G, Chanock SJ, Gu FY, Hankinson SE, Hunter DJ, Hofman A, Tiemeier H, Uitterlinden AG, van Duijn CM, Walter S, Chasman DI, Everett BM, Pare G, Ridker PM, Li MD, Maes HH, Audrain-McGovern J, Posthuma D, Thornton LM, Lerman C, Kaprio J, Rose JE, Ioannidis JPA, Kraft P, Lin DY, Sullivan PF

Publication type: Letter

Publication status: Published

Journal: Nature Genetics

Year: 2010

Volume: 42

Issue: 5

Pages: 441-447

Print publication date: 25/04/2010

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718



DOI: 10.1038/ng.571