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

H. Furberg, Y.J. Kim, J. Dackor, E. Boerwinkle, N. Franceschini, D. Ardissino, L. Bernardinelli, P.M. Mannucci, F. Mauri, P.A. Merlini, B.W.J.H. Penninx, J.H. Smit, N. Vogelzangs, D.I. Boomsma, E.J.C. de Geus, J.M. Vink, G. Willemsen, H. Tiemeier, A.G. Uitterlinden, C.M. van DuijnH.H. Maes, J. Audrain-McGovern, D. Posthuma, L.M. Thornton, C. Lerman, J. Kaprio, J.E. Rose, J.P.A. Ioannidis, P. Kraft, D.-Y. Lin, P.F. Sullivan

Research output: Contribution to JournalArticleAcademicpeer-review

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. © 2010 Nature America, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)441-447
Number of pages7
JournalNature Genetics
Volume42
Issue number5
Early online date25 Apr 2010
DOIs
Publication statusPublished - May 2010

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