title: Genome-wide meta-analyses of smoking behaviors in African Americans.
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.
authors: Center for Health Sciences, Policy Division, SRI International, Menlo Park, CA, USA. spdavid@stanford.edu
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mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D012907:Smoking / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D011978:Receptors, Nicotinic; C504404:SPOCK2 protein, human