Elucidating psychosocial outcome profiles as a function of aggregate genetic risk for suicide attempt and alcohol use disorder.

Genetic factors contribute to alcohol use disorder (AUD) and suicide attempt (SA) co-occurrence. Whether individuals with high genetic liability to one outcome versus the other, or to both, differ in terms of their risk for other psychosocial outcomes is unexplored. To this end, the authors conducted a cohort study of Swedish individuals born 1965-1985, with follow-up through December 31, 2018. Using deciles of family genetic risk scores (FGRS), a measure of aggregate genetic liability, they characterized individuals as being in a "risk" group with high/low FGRS or a "reference" with median FGRS. Within each of five comparisons, they calculated correlations between genetic profile and psychosocial outcomes. Groups included up to N = 536 312 individuals. The mean (SD) age at end of follow-up was 44.1 (6.1) years. High genetic liability to both AUD and SA was most prominently correlated with negative outcomes, e.g., r = 0.51 for drug use disorder. High FGRSSA or FGRSAUD, irrespective of genetic loading for the other, was less strongly correlated with negative outcomes, as was having high FGRSAUD but low FGRSSA. The risk subsample with high FGRSSA and low FGRSAUD were least likely to experience negative outcomes (r < 0.1) and more likely to exhibit positive educational outcomes (r≥0.1) relative to their reference subsample. These analyses indicate that aggregate genetic risk profiles for AUD and SA are differentially correlated with a range of negative psychosocial outcomes. Having low genetic liability to AUD is potentially protective for some outcomes even alongside elevated SA risk. These findings underscore the imperative for further genetic dissection of these frequently comorbid conditions.