Polygenic risk scores in relation to suicidality among youth with or at risk for bipolar disorder

Abstract

Purpose: The risk of suicide among individuals with bipolar disorder (BD) is among the highest of all psychiatric disorders. The etiology of suicidality is complex and multifactorial, with genetic factors playing a prominent role according to twin-, family-, and molecular genetic studies. This study examines polygenic risk scores from adult studies in relation to suicidality in youth with or at risk for BD.

Methods: Primary analyses examined the association of polygenic risk scores for suicide attempt, based on adult genome-wide association study data, with suicidal ideation, self-harm, and suicide attempt in 232 youth (mean age 16.7 years), including 125 with, and 107 at high-risk for, BD. We also tested polygenic risk scores for risk tolerance, schizophrenia, major depressive disorder, BD, and attention-deficit hyperactivity disorder in secondary analyses.

Results: Polygenic risk scores for suicide attempt were not significantly associated with suicidal ideation, self-harm, or suicide attempt. Higher polygenic risk scores for major depressive disorder were nominally associated with increased risk of suicidal ideation in the overall sample (beta = 0.36, se(beta) = 0.16, p = 0.017), controlling for covariates.

Implications: Our finding that polygenic risk for depression is associated with suicidal ideation converges with prior findings in youth and adults. While present findings are constrained by sample size, they underscore the importance of undertaking genome-wide association studies in youth, rather than relying solely on prior adult genome-wide association studies.

Keywords: Bipolar disorder; Polygenic risk scores; Self-harm; Suicidal ideation; Suicide attempt; Youth.