Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk

Background: Suicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI). Methods: We used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA. Results: In the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13–1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04–1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI. Conclusions: PRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA. Limitations: At present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations.