Genome-wide association studies identify polygenic effects for completed suicide in the Japanese population

Area of Science:

• Genetics
• Psychiatry
• Public Health

Background:

• Suicide is a major global public health issue, with high rates in some Asian countries like Japan.
• Previous studies suggest significant genetic heritability for suicide, but research in non-European populations is limited.
• Challenges in sample collection from individuals who died by suicide hinder genetic studies.

Purpose of the Study:

• To conduct the first genome-wide association study (GWAS) for suicidal behavior in a Japanese population.
• To investigate the genetic heritability and shared genetic risk factors for completed suicide.
• To explore the polygenic architecture underlying completed suicide in East Asians.

Main Methods:

• Genome-wide association studies (GWAS) were performed on two independent Japanese datasets.
• The study included a total of 746 suicide cases and 14,049 non-suicide controls.
• Genomic restricted maximum likelihood (GREML) and polygenic risk score (PRS) analyses were utilized.

Main Results:

• No genome-wide significant single-nucleotide polymorphisms (SNPs) were identified.
• Significant SNP-based heritability for completed suicide was demonstrated (35-48%, P < 0.001).
• A highly significant shared genetic risk was found between the two datasets (Pbest = 2.7 × 10⁻¹³).

Conclusions:

• Completed suicide exhibits significant SNP-based heritability in the Japanese population.
• The findings provide evidence for a polygenic architecture underlying completed suicide.
• This study is the first GWAS of suicidal behavior in an East Asian population, highlighting genetic contributions.