29. ELUCIDATING PSYCHOSOCIAL OUTCOME PROFILES AS A FUNCTION OF AGGREGATE GENETIC RISK FOR SUICIDE ATTEMPT AND ALCOHOL USE DISORDER

Background 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. Elucidation of such differences could help health care providers better understand psychosocial risks of these genetic profiles. Methods We 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, we characterized individuals as being in a “risk” group with high/low FGRS or a “reference” with median FGRS, defining five groups: (i) High AUD-G (where the “G” denotes genetic risk); (ii) High SA-G; (iii) High AUD-G/High SA-G; (iv) High AUD-G/Low SA-G; and (v) Low AUD-G/High SA-G. Within each of these five comparison groups, we calculated correlations between genetic profile status and psychosocial outcomes, including academic achievement, socioeconomic measures, and registrations for psychiatric illness. Results Group sized ranged from N=151,152 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 strongly correlated with negative outcomes, e.g., r=0.51 for drug use disorder. High FGRS for SA or AUD, irrespective of genetic loading for the other, was less strongly correlated with negative outcomes, as was having high FGRS for AUD but low FGRS for SA. The risk subsample of the Low AUD-G/High SA-G group was 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. Follow-up analyses indicated that the results in this group were likely driven by the selection for low AUD FGRS. Discussion 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.