A genome-wide association study of attempted suicide

Area of Science:

• Psychiatric Genetics
• Genomics
• Molecular Psychiatry

Background:

• Heritable factors contribute to suicide attempts, some linked to psychiatric disorders and others independent.
• Previous linkage studies identified regions on 2p11-12 and 6q25-26 for attempted suicide.
• Higher resolution methods like genome-wide association studies (GWAS) are needed to discover additional genetic loci.

Purpose of the Study:

• To conduct a genome-wide association study (GWAS) for attempted suicide in bipolar disorder.
• To identify single-nucleotide polymorphisms (SNPs) associated with suicide attempts in bipolar subjects.

Main Methods:

• Compared SNP genotypes of 1201 bipolar (BP) subjects with suicide attempts to 1497 BP subjects without attempts.
• Identified 2507 SNPs associated at P<0.001 and tested them in an independent replication sample.
• Performed combined analysis of discovery and replication sets to assess genome-wide significance.

Main Results:

• Initially identified 2507 associated SNPs, none significant after replication and multiple testing correction.
• Combined analysis revealed a genome-wide significant association signal on chromosome 2p25 (rs300774).
• Associated SNPs on 2p25 are within a linkage disequilibrium block containing the ACP1 gene, which is upregulated in completed suicide cases and influences Wnt signaling.

Conclusions:

• A significant genetic association signal for attempted suicide in bipolar disorder was detected on chromosome 2p25, near the ACP1 gene.
• ACP1, a tyrosine phosphatase influencing Wnt signaling, is a functional candidate gene for suicide attempt risk.
• Larger GWAS sample sizes are required to confirm the 2p25 signal and identify further genetic risk factors for attempted suicide.