SEX DIFFERENCES IN ASSOCIATIONS BETWEEN PERSONALITY POLYGENIC RISK SCORES AND HAZARDOUS ALCOHOL USE

Prior twin research has indicated that, on average, 40% of observed variation in personality traits can be explained by additive genetic influence. Additionally, twin and molecular genetic studies have also suggested that... [ view full abstract ]

Prior twin research has indicated that, on average, 40% of observed variation in personality traits can be explained by additive genetic influence. Additionally, twin and molecular genetic studies have also suggested that specific personality traits found to be associated with hazardous alcohol use or the development of alcohol use disorders (AUD) may represent tractable endophenotypes for investigating the shared underlying etiology between psychiatric disorders. Specifically, characteristics of personality including impulsivity, risk-taking, sensation-seeking as well as neuroticism, extraversion and low conscientiousness have been identified in research examining the relations between individual personality traits and hazardous binge drinking phenotypes. However, these associations have been shown be moderated by several factors including drinking motives, alcohol expectancies and sex. Expanding on prior research, the present study examined potential sex differences in the associations between cumulative genetic influence for risk-taking and the Big Five personality traits (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism) and hazardous alcohol use quantified by lifetime maximum drinks in 24-hours, DSM-5 AUD symptom count, alcohol-induced blackout, and drinking to intoxication 2-3 times per week. GWAS summary data from the UK Biobank project and the Genetics of Personality Consortium were used to calculate polygenic risk scores (PRSs) for risk-taking, and the Big Five personality traits, respectively. PRSs were calculated in an independent Caucasian sample of 1,685 related individuals (62.6% female) collected as part of the UCSF Family Alcoholism Study. Genotype data were obtained from low-coverage whole genome sequencing and a linear mixed modeling approach was used to predict alcohol use phenotypes from personality PRSs for the total sample and for males and females separately. Ancestry estimates derived from principal components analysis were included as covariates to account for population sub-structure. For the overall sample, risk-taking PRSs at a range of variant inclusion significance thresholds (p < .50-<.10) were significantly associated with drinking to intoxication 2-3 times per week and experiencing 3 or more lifetime alcohol-induced blackouts, neuroticism PRSs (p < .50-<.10) were significantly associated with maximum number of drinks in 24-hours, and extraversion PRSs (p < .50-<.20) showed a significant negative association with 3 or more lifetime alcohol-induced blackouts such that those with lower extraversion risk scores were more likely to have experienced 3 or more blackouts. When modeled separately based on sex, associations between risk-taking PRSs and regular drinking to intoxication and extraversion PRSs and blackouts were significant in females, while only the association between risk-taking PRSs and blackouts were significant in males. Additionally, significant interactions between risk-taking PRSs and sex were observed for the prediction of both maximum number of drinks (p < .05) and having 3 or more blackouts (p <.50-<.20), and a significant interaction between extraversion PRSs at the p < .001 threshold and sex suggested that males with higher extraversion scores were more likely to have experienced 3 or more blackouts while the opposite was true for female individuals. These findings extend previous research by suggesting that associations between genetic influences on personality and problematic alcohol use may be sex and phenotype-specific.