학술논문

Genome-wide meta-analyses of smoking behaviors in African Americans.
Document Type
article
Source
Translational psychiatry. 2(5)
Subject
Chromosomes
Human
Pair 10
Chromosomes
Human
Pair 15
Humans
Genetic Predisposition to Disease
Proteoglycans
Receptors
Nicotinic
Nerve Tissue Proteins
Smoking
Genotype
Phenotype
Polymorphism
Single Nucleotide
Adult
Aged
Middle Aged
African Americans
Female
Male
Statistics as Topic
Genetic Variation
Genome-Wide Association Study
Genetic Loci
African American
genome-wide association
health disparities
nicotine
smoking
tobacco
Chromosomes
Human
Pair 10
Pair 15
Polymorphism
Single Nucleotide
Receptors
Nicotinic
Clinical Sciences
Public Health and Health Services
Psychology
Language
Abstract
The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.