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

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.

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.

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.

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.