Journal
MOLECULAR PSYCHIATRY
Volume 13, Issue 4, Pages 368-373Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4002154
Keywords
cigarette smoking; nicotine dependence; genetic association; nicotinic receptor subunit; whole genome association
Funding
- NIDA NIH HHS [P60 DA005186, P60 DA005186-210018] Funding Source: Medline
- PHS HHS [P60 05186] Funding Source: Medline
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Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these similar to 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P = 6.9 x 10(-5)). In a third set of European populations (n = similar to 7500) which had been genotyped for similar to 6000 SNPs in similar to 2000 genes, an allele in the same haplotype was associated with CPD (nominal P = 2.6 x 10(-6)). These results (in three independent populations of European origin, totaling similar to 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND.
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