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

Liu et al., 2010 | Nat Genet | Meta Analysis

Citation

Liu Jason Z, Tozzi Federica, ... Marchini Jonathan. Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nat Genet. 2010-May;42(5):436-40. doi:10.1038/ng.572

Abstract

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

Key Findings

Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

Outcomes Measured

Requires manual extraction

Population

Field	Value
Population	See abstract
Sample Size	41150
Age Range	See abstract
Condition	See abstract

MeSH Terms

Adult
Aged
Alleles
Chromosome Mapping
Chromosomes, Human, Pair 15
Cohort Studies
Female
Genetic Markers
Genome, Human
Humans
Male
Middle Aged
Models, Genetic
Neurons
Polymorphism, Single Nucleotide
Receptors, Nicotinic
Smoking

Evidence Classification

Level: Meta Analysis
Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
Vertical: niacin

Provenance

PMID: 20418889
DOI: 10.1038/ng.572
PMCID: PMC3612983
Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09