67 - GENOME-WIDE ASSOCIATION STUDY OF SUICIDE ATTEMPT IN MAJOR PSYCHIATRIC DISORDERS

Abstract

Background Suicide is a worldwide public health problem and the second leading cause of death among young adults. Over 90% of suicide attempters or victims have a psychiatric diagnosis, particularly mood disorders. However, twin and family studies suggest that the genetic aetiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. Genome-Wide Association Studies (GWAS) to date have failed to identify replicable genetic associations with suicide attempt, likely due to limited sample size, although these studies have indicated that suicide attempt has a polygenic architecture. Here, we present the largest GWAS on suicide attempt to date, using cohorts of patients with Major Depressive Disorder (MDD), Bipolar Disorder (BIP) and Schizophrenia (SCZ), recruited from the Psychiatric Genomics Consortium. Methods Samples comprise 1624 suicide attempters and 8789 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1685 attempters and 2948 non-attempters with SCZ. GWAS on suicide attempt were performed by comparing suicide attempters versus non-attempters in each psychiatric disorder and then conducting meta-analysis between them. To further explore the genetic architecture of suicide attempt, polygenic risk scoring was used to test for pleiotropy between suicide attempt in these psychiatric disorders. Results Three genome-wide significant loci for suicide attempt were found: one in the GWAS of suicide attempt in MDD (rs45593736, P = 2.57 × 10-8, OR A allele = 2.37), one in the GWAS of suicide attempt in BIP, which strengthened in the meta-analysis of suicide attempt in mood disorders (top SNP rs28591567, P = 3.11 × 10-8, OR A allele 0.83) and an additional locus in the meta-analysis of suicide attempt in mood disorders (rs138689899, P = 2.74 × 10-8, OR T allele = 1.75). There were no significant associations with suicide attempt in SCZ or in the meta-analysis of suicide attempt across all three disorders. Initial results using polygenic risk scoring provide no evidence of pleiotropy between suicide attempt in these psychiatric disorders. Discussion These genome-wide significant loci for suicide attempt are currently being replicated in independent samples. The results of this study suggest a difference in the genetic aetiology of depressive versus psychotic suicide attempts. Polygenic risk scoring is a useful approach to test for pleiotropy and inform the design of future genetic studies.