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Genome-wide meta-analyses identify multiple loci associated with smoking behavior.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Genome-wide meta-analyses identify multiple loci associated with smoking behavior. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Corporate/Institutional Authors | Tobacco and Genetics Consortium, |
| Journal | Nat Genet |
| Volume | 42 |
| Issue | 5 |
| Pagination | 441-7 |
| Date Published | 2010 May |
| ISSN | 1546-1718 |
| Keywords | Age Factors, Alleles, Chromosome Mapping, Female, Genome, Genome-Wide Association Study, Genotype, Humans, Male, Molecular Epidemiology, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Receptors, Nicotinic, Smoking |
| Abstract | <p>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.</p> |
| DOI | 10.1038/ng.571 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 20418890 |
| PubMed Central ID | PMC2914600 |
| Grant List | R01 CA082659 / CA / NCI NIH HHS / United States K07 CA118412 / CA / NCI NIH HHS / United States R01 HL087647 / HL / NHLBI NIH HHS / United States U01 HL054527 / HL / NHLBI NIH HHS / United States K07 CA118412-04 / CA / NCI NIH HHS / United States R01 DK072193 / DK / NIDDK NIH HHS / United States R01 DA012844 / DA / NIDA NIH HHS / United States |