Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.
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DOI:
10.1038/ng.572
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发表时间:
2010-05
期刊:
影响因子:
30.8
通讯作者:
--
中科院分区:
生物学1区
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--
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Smoking is a leading global cause of disease and mortality. We performed a genomewide meta-analytic association study of smoking-related behavioral traits in a total sample of 41,150 individuals drawn from 20 disease, population, and control cohorts. Our analysis confirmed an effect on smoking quantity (SQ) at a locus on 15q25 (P=9.45e-19) that includes three genes encoding neuronal nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3, CHRNB4). We used data from the 1000 Genomes project to investigate the region using imputation, which allowed analysis of virtually all common variants in the region and offered a five-fold increase in coverage over the HapMap. This increased the spectrum of potentially causal single nucleotide polymorphisms (SNPs), which included a novel SNP that showed the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.
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