Suicidality phenotypes reflect both shared and distinct genetic factors.

Area of Science:

• Psychiatric Genetics
• Human Genomics
• Behavioral Science

Background:

• Suicidality phenotypes, including suicidal ideation (SI), non-fatal suicide attempt (SA), and suicide death (SD), are known to be heritable.
• Both shared and phenotype-specific genetic influences contribute to the complex etiology of suicidality.

Purpose of the Study:

• To investigate the shared genetic architecture across different suicidality phenotypes using genomic structural equation modeling.
• To conduct a multivariate genome-wide association study (GWAS) of a latent suicidality factor.
• To identify novel genetic loci associated with suicidality and explore phenotype-specific genetic influences.

Main Methods:

• Genomic structural equation modeling was employed to estimate shared genetic architecture across GWAS data for SI, SA, and SD.
• A multivariate GWAS was performed on a latent suicidality factor derived from these phenotypes.
• Follow-up analyses examined residual genetic variance specific to each phenotype and conditioned on genetic liability to psychiatric disorders.

Main Results:

• The study identified 36 genome-wide significant loci associated with suicidality, with seven loci being novel discoveries.
• Residual genetic variance specific to each phenotype was identified, including three SD-specific genomic risk loci.
• Significant residual genetic variance was observed across SI, SA, SD, and the common suicidality factor when conditioned on genetic liability to psychiatric disorders.

Conclusions:

• Suicidality arises from a complex interplay of shared genetic liability and phenotype-specific genetic contributions.
• The findings advance our understanding of the genetic architecture of suicidality and may inform future targeted interventions.
• Identifying specific genetic risk loci contributes to a more nuanced understanding of the biological underpinnings of suicide-related behaviors.