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

Abstract

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. 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.

Biomarker discovery in attention deficit hyperactivity disorder: RNA sequencing of whole blood in discordant twin and case-controlled cohorts

“…Inhibition of FAM134A causes impaired proteostasis in the endoplasmic reticulum due to the accumulation of misfolded proteins, which has been implicated in vascular dementia [ 45 ]. FAM162A is associated by GWAS to a gene-by-alcohol dependence interaction study of risky sexual behaviors and so it could be related to behavioral control [ 46 ]. Coincidentally, ADHD is associated with increased sexual risk taking [ 47 ].…”

Nuclear transcriptional changes in hypothalamus of Pomc enhancer knockout mice after excessive alcohol drinking

“…Here we unexpectedly observed a profound decrease of Avpi1 transcript levels in the nPE1 +/+ hypothalamus after chronic alcohol drinking (Figure D), suggesting for the first time the potential interaction between the AVP‐induced protein 1 and excessive alcohol drinking or withdrawal. Of interest, in a recent human genetic study, rs7913179 variant in the Avpi1 gene is found to associate with alcohol dependency in a genome‐wide gene‐by‐alcohol dependence interaction analysis in European men . Although the AVP/V1b receptor system plays important roles in alcohol drinking, it seems unknown, however, whether and how the hypothalamic AVP‐induced protein 1 is involved in alcohol drinking behaviors, and further study is needed.…”

“…Of interest, in a recent human genetic study, rs7913179 variant in the Avpi1 gene is found to associate with alcohol dependency in a genome-wide gene-by-alcohol dependence interaction analysis in European men. 53 Although the AVP/V1b receptor system plays important roles in alcohol drinking, 11,15 it seems unknown, however, whether and how the hypothalamic AVP-induced protein 1 is involved in alcohol drinking behaviors, and further study is needed.…”

Biomarker Discovery in Attention Deficit Hyperactivity Disorder: RNA sequencing of Whole Blood in Discordant Twin and Case-Controlled Cohorts

“…Inhibition of FAM134A causes impaired proteostasis in the endoplasmic reticulum due to the accumulation of misfolded proteins, which has been implicated in vascular dementia [45]. FAM162A is associated by GWAS to a gene-by-alcohol dependence interaction study of risky sexual behaviors and so it could be related to behavioral control [46]. Coincidentally, ADHD is associated with increased sexual risk taking [47].…”