Genome‐wide association study of body mass index in subjects with alcohol dependence

Abstract

Outcomes related to disordered metabolism are common in alcohol dependence (AD). To investigate alterations in the regulation of body mass that occur in the context of AD, we performed a GWAS of BMI in African-Americans (AAs) and European-Americans (EAs) with AD. Subjects were recruited for genetic studies of alcohol or drug dependence, and evaluated using the Semi-Structured Assessment for Drug Dependence and Alcoholism. We investigated a total of 2,587 AAs and 2,959 EAs with DSM-IV AD diagnosis. In the stage-1 sample (N=4,137), we observed three genome-wide significant (GWS) SNP associations, rs200889048 (p=8.98*10−12) and rs12490016 (p=1.44*10−8) in EAs, and rs1630623 (p=5.14*10−9) in AAs and EAs meta-analyzed. In the stage-2 sample (N=1,409), we replicated 278, 253, and 168 of the stage-1 suggestive loci (p<5*10−4) in AAs, EAs, and AAs and EAs meta-analyzed, respectively. A meta-analysis of stage-1 and stage-2 samples (N=5,546) identified two additional GWS signals: rs28562191 in EAs (p=4.46*10−8) and rs56950471 in AAs (p=1.57*10−9). Three of the GWS loci identified (rs200889048, rs12490016, rs1630623) were not previously reported by GWAS of BMI in the general population and two of them raise interesting hypotheses: rs12490016 – a regulatory variant located within LINC00880, where there are other GWAS-identified variants associated with birth size, adiposity in newborns, and bulimia symptoms which also interact with social stress in relation to birth size; rs1630623 – a regulatory variant related to ALDH1A1, a gene involved in alcohol metabolism and adipocyte plasticity. These loci offer molecular insights regarding the regulatory mechanisms of body mass in the context of AD.

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

“…A Mendelian randomization study in 261 991 individuals of European descent indicated that carriers of the ADH1B rs1229984 protective allele have a more favorable cardiovascular profile (Holmes et al, 2014). Furthermore, our recent GWAS of BMI in subjects with alcohol dependence showed that an alcohol-metabolism gene (in that case, ALDH1A1) could be involved in the regulation of body mass in the context of alcohol dependence (Polimanti et al, 2015b). These findings support a relationship between alcohol-metabolism gene variants with cardiovascular and metabolic conditions.…”

The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene

“…However, there is very little available information on the molecular mechanisms by which alcohol-related behaviors contribute to RSB. Genomewide analysis can be a powerful tool to identify molecular mechanisms of complex traits, including in the context of alcohol abuse (Polimanti et al, 2015). Although no large genomic investigation has been conducted on RSB, a recent genome-wide association study (GWAS) of age at first sexual intercourse indicated that the onset of sexual activity is genetically correlated to other reproductive and behavioral traits (Day et al, 2016).…”

Predicting risk for Alcohol Use Disorder using longitudinal data with multimodal biomarkers and family history: a machine learning study

“…In this paper we present a supervised ML method (SVM) to classify individuals before AUD emerged into those who developed AUD years later and those who did not. The analysis incorporates EEG measures, FH information, and data on a set of SNPs derived from recent GWAS of alcohol consumption 12,13 , alcohol dependence 14,15 , and alcohol-related EEG measures 15,16 , as features. An essential aspect of identifying a true classifier is to control for possible effects of confounding variables such as age 17,18 , gender 19,20 , and ancestry 21,22 which can lead to misclassification of the model 23 .…”