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- Title
Genome-wide meta-analyses identify multiple loci associated with smoking behavior.
- Authors
Furberg, Helena; YunJung Kim; Dackor, Jennifer; Boerwinkle, Eric; Franceschini, Nora; Ardissino, Diego; Bernardinelli, Luisa; Mannucci, Pier M.; Mauri, Francesco; Merlini, Piera A.; Absher, Devin; Assimes, Themistocles L.; Fortmann, Stephen P.; Iribarren, Carlos; Knowles, Joshua W.; Quertermous, Thomas; Ferrucci, Luigi; Tanaka, Toshiko; Bis, Joshua C.; Furberg, Curt D.
- Abstract
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.
- Publication
Nature Genetics, 2010, Vol 42, Issue 5, p441
- ISSN
1061-4036
- Publication type
Academic Journal
- DOI
10.1038/ng.571