Leveraging Family Genetic Risk Scores to Understand the Etiology of Suicidal Behaviors and Their Associations With...

Suicidal behaviors are complex phenotypes, often studied in the context of psychiatric comorbidities. However, little is known about the specific roles of psychiatric disorders and the etiology of suicidal behaviors that occur outside the context of psychiatric comorbidities.

We included 926,040 individuals born 1980-1990 from the Swedish national registries. We conducted separate analyses for suicide attempt (SA) and suicide death (SD) and first tested whether family genetic risk scores (FGRS) for SA and SD differed across individuals with versus without a registration for psychiatric disorders. We then performed Cox proportional hazards models to evaluate the main effects of psychiatric disorders (alcohol use disorder, major depression, anxiety disorders, drug use disorders, attention-deficit/hyperactivity disorder) in risk of SA/SD, and their interaction with genetic liability (FGRS). The interaction was introduced to evaluate potential differential effects of genetic risk in those with versus without a prior psychiatric comorbidity.

Only ~30% of individuals registered for SA/SD had a prior psychiatric diagnosis. FGRS for SA/SD was higher in those with prior psychiatric disorders. All psychiatric comorbidities were significantly related to SA (HRs 4.61-9.03) and SD (HRs 8.06-15.90). Interaction analyses indicated that, in those with no prior psychiatric disorder, the effect of genetic liability on SA/SD was higher.

Though psychiatric disorders were associated with increased risk of SA/SD, a substantial proportion of suicidal behaviors occurred outside the context of psychiatric disorders, urging the development of screening and prevention in non-psychiatric populations. Despite their low genetic liability for SA/SD, findings suggest that the effect of genetic risk on SA/SD risk is stronger in those with no psychiatric comorbidity.