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.

Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women

“…As previously observed (The Tobacco and Genetics Consortium, 2010), CHRNA3-CHRNA5 rs8034191, rs1051730, and rs16969968 were strongly associated with smoking quantity (ie, cigarettes per day) in European subjects. We also replicated the association of CHRNA5 rs2036527 with the same trait in the AFR sample, consistent with results from a large GWAS of smoking quantity in African-American subjects (David et al, 2012). Unfortunately, we were not able to replicate the associations of CHRNA5 rs12914385, likely because the genotypes for this variant were not available for the PAGE WHI cohort and therefore the data were available in only 36% of the total sample (2% of the total EUR sample).…”

“…We chose these variants on the basis of numerous GWAS (Gelernter et al, 2014;Xu et al, 2015) and candidate-locus studies (Sherva et al, 2010;Hart et al, 2015;Jensen et al, 2015), and a recent meta-analysis of genetic studies of nicotine and alcohol traits (Buhler et al, 2015) and GWAS performed previously in different population groups (David et al, 2012;Gelernter et al, 2014).…”

“…It is also recognized that the ADH1B locus is under strong selection in East Asians and a recent study hypothesized an independent evolution of the same locus also in Europeans (Galinsky et al, 2016). For smoking behaviors, the most recognized risk locus is the CHRNA3-CHRNA5-CHRNB4 gene cluster, and risk alleles in this region (rs8034191, rs1051730, rs12914385, rs2036527, and rs16969968) are associated with smoking behaviors including nicotine dependence and smoking quantity (The Tobacco and Genetics Consortium, 2010;David et al, 2012). On the molecular level, these genetic variants are associated with functional alterations in subunits of nicotinic acetylcholine receptors, reducing their activity and the aversive effects of nicotine (Wen et al, 2016).…”

A Whole-Blood Transcriptome Meta-Analysis Identifies Gene Expression Signatures of Cigarette Smoking

“…Previous studies have reported a genetic predisposition (8)(9)(10)(11) to cigarette smoking. Other studies have reported smokingrelated DNA methylation patterns (12)(13)(14)(15)(16)(17)(18).…”

Gene-Environment Interplay and Substance Use: A Review of Recent Findings

“…Genome-wide association studies (GWAS) and meta-analyses of GWAS have identified single nucleotide polymorphisms (SNPs) that are associated with alcohol dependence and smoking phenotypes [7][8][9]. In a review of these and candidate gene studies, Bühler et al [10•] reported that the most robust associations involve SNPs in the alcohol metabolizing genes, the cholinergic gene cluster, and in the dopamine D2 receptor (DRD2) and Ankyrin repeat and kinase domain containing 1 (ANNK1) genes.…”