Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.

We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis. A total of 2,173 African-American (AA) and 1,751 European-American (EA) subjects were investigated. Information regarding RSB (lifetime experiences of unprotected sex and multiple sexual partners) and DSM-IV diagnosis of lifetime AD were derived from the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). In our ancestry- and sex-specific analyses, we identified four independent genome-wide significant (GWS) loci (p < 5*10-8 ) and one suggestive locus (p < 6*10-8 ). In men, we observed a GWS signal in FAM162A (rs2002594, p = 4.96*10-8 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10-8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10-9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10-8 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10-10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric illness and personality features, suggesting that the interplay between AD and RSB is mediated by alleles associated with behavioral traits.

454 African American women cases, 1,087 African American men cases, 444 European ancestry women cases, 992 European ancestry men cases, 231 African American women controls, 401 African American men controls, 142 European ancestry women controls, 173 European ancestry men controls