Associations between cumulative genetic influence for risk-taking and hazardous alcohol use in two independent samples
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI-COLUMBIA AT AUTHOR'S REQUEST.] A propensity for risk-taking may be associated with hazardous alcohol-related behaviors especially in men. Prior research indicating substantial heritability and genetic overlap for risk-taking and disordered alcohol use suggests that risk-taking may function as an endophenotype for more complex hazardous drinking behaviors. The current study aimed to examine the associations between polygenic risk scores (PRSs) for risk-taking and hazardous alcohol use phenotypes in two independent samples: a young adult, moderate drinking sample and a middle-aged, heavy drinking family-based sample. Genome-wide association summary results from the UK Biobank project were used to calculate risk-taking PRSs which were then used to predict hazardous alcohol use phenotypes in both samples. Possible sex-specific associations were examined using PRS-by-sex interaction models. Results indicated significant relations between PRSs and experiencing blackouts and regular intoxication in the older heavy-drinking sample and between PRSs and experiencing blackouts in an older sub-group of young adults. Strong evidence for sex-specific associations were not supported. These results build on prior studies by demonstrating that genetic influence for a risk-taking endophenotype may confer risk for specific hazardous alcohol use outcomes and may exert a greater effect in the absence of strong environmental influences or in the presence of heavier drinking. Findings also underscore the importance of specific hazardous alcohol use phenotypes for genetics research above and beyond general measures of consumption or disordered use.
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