Genetic architecture and risk of suicide attempt across neurodevelopmental and psychiatric conditions.

Abstract

Background: Suicide attempt (SA) is prevalent among individuals with neurodevelopmental and psychiatric conditions, yet similarities and differences in the genetic architecture of SA across these conditions remain unclear.

Methods: In the iPSYCH cohort (N=98,069), SA was identified using ICD-10 codes among individuals diagnosed with attention-deficit hyperactivity disorder (ADHD) (N=22,962), autism (N=17,670), schizophrenia (N=5,974), bipolar disorder (N=3,028), depression (N=28,844), and controls (N=34,049). We evaluated 21 polygenic scores (PGSs) in individuals with and without SA within each diagnosis, stratified individuals into PGS quantiles, estimated absolute SA risk, and conducted sex-stratified analyses.

Results: SA was 1% among controls but ranged from 5% in autism to 31% in schizophrenia. Several PGSs were increased in individuals with SA across diagnoses, including PGS for ADHD, depression, and substance use disorders (SUD). SA-PGS stratification showed marked SA absolute risk differences, e.g., 40% in the top PGS tertile vs 29% in the lowest tertile in schizophrenia. PGS-loads did not differ between females and males with SA across diagnoses. However, absolute SA risk differed substantially. In the highest SA-PGS tertile in ADHD, the absolute SA risk reached 36% for females and 22% for males and was further increased to 48% in those with comorbid SUD.

Conclusions: SA genetic architecture is similar across neurodevelopmental and psychiatric conditions and individuals can be stratified into SA risk groups based on PGSs, and co-occuring SUD. Being a female or having comorbid SUD are strong risk factors for SA, however SA common variants, still affect SA risk in the presence of those factors.