TY - JOUR
T1 - Genome-wide meta-analyses identify multiple loci associated with smoking behavior
AU - Furberg, H.
AU - Kim, Y.J.
AU - Dackor, J.
AU - Boerwinkle, E.
AU - Franceschini, N.
AU - Ardissino, D.
AU - Bernardinelli, L.
AU - Mannucci, P.M.
AU - Mauri, F.
AU - Merlini, P.A.
AU - Penninx, B.W.J.H.
AU - Smit, J.H.
AU - Vogelzangs, N.
AU - Boomsma, D.I.
AU - de Geus, E.J.C.
AU - Vink, J.M.
AU - Willemsen, G.
AU - Tiemeier, H.
AU - Uitterlinden, A.G.
AU - van Duijn, C.M.
AU - Maes, H.H.
AU - Audrain-McGovern, J.
AU - Posthuma, D.
AU - Thornton, L.M.
AU - Lerman, C.
AU - Kaprio, J.
AU - Rose, J.E.
AU - Ioannidis, J.P.A.
AU - Kraft, P.
AU - Lin, D.-Y.
AU - Sullivan, P.F.
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
U2 - 10.1038/ng.571
DO - 10.1038/ng.571
M3 - Article
SN - 1061-4036
VL - 42
SP - 441
EP - 447
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -
