02260nas a2200325 4500008004100000022001400041245008700055210006900142260001300211300001000224490000700234520135200241653001601593653001201609653002301621653001101644653001101655653003401666653001301700653001101713653000901724653002701733653001501760653001401775653003601789653002501825653001201850110003601862856003601898 2010 eng d a1546-171800aGenome-wide meta-analyses identify multiple loci associated with smoking behavior.0 aGenomewide metaanalyses identify multiple loci associated with s c2010 May a441-70 v423 a
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], 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.
10aAge Factors10aAlleles10aChromosome Mapping10aFemale10aGenome10aGenome-Wide Association Study10aGenotype10aHumans10aMale10aMolecular Epidemiology10aOdds Ratio10aPhenotype10aPolymorphism, Single Nucleotide10aReceptors, Nicotinic10aSmoking1 aTobacco and Genetics Consortium uhttps://chs-nhlbi.org/node/1191