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Polygenic Risk, Trait Variables, and External Stressors in Fatal and Nonfatal Suicidal Behavior
Min Ji Kim1,2, Hanga Galfalvy2,3, Tarjinder Singh1,2,4
1Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York.
JAMA Network Open
|January 15, 2026
Summary
Genetic predisposition for suicide attempts is linked to clinical traits and environmental stressors. Understanding these interactions is crucial for developing targeted interventions for suicidal behavior.
Area of Science:
- Psychiatry
- Genetics
- Epidemiology
Background:
- Suicidal behavior has a significant heritable component.
- Understanding genetic and environmental influences is key for targeted interventions.
Purpose of the Study:
- To investigate the interplay between polygenic scores for suicide attempt (suicide-PGS), clinical characteristics, and external stressors in suicidal behavior.
Main Methods:
- A case-control study involving genome-wide genotyping of individuals with and without suicidal behavior.
- Analysis of associations between suicide-PGS, internal traits (aggression, hostility, impulsivity), clinical variables (depression, suicidal ideation), and external stressors (childhood abuse, life events).
Main Results:
- Suicide-PGS was associated with suicide attempts in both live and postmortem cohorts.
- Higher suicide-PGS correlated with aggression severity, depression severity, and increased depressive episodes in live attempters.
- Suicide-PGS also associated with childhood abuse and recent life stress, but these did not moderate genetic associations.
Conclusions:
- Genetic liability for suicide attempt interacts with clinical characteristics and environmental factors.
- Further research with larger sample sizes and detailed phenotyping is necessary to fully elucidate genetic-environment contributions to suicide risk.
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