Association analysis between suicidal behaviour and candidate genes of bipolar disorder and schizophrenia

Abstract

Background: The present study investigated associations between the strongest joint genetic risk variants for bipolar disorder (BD) and schizophrenia (SCZ) and a history of suicide attempt in patients with BD, SCZ and related psychiatric disorders. Methods: A history of suicide attempt was assessed in a sample of 1009 patients with BD, SCZ and related psychosis spectrum disorders, and associations with the joint genetic risk variants for BD and SCZ (rs2239547 (ITIH3/4-region), rs10994359 (ANK3) and rs4765905 (CACNA1 C)) were investigated. Previously reported susceptibility loci for suicide attempt in BD were also investigated. Associations were tested by logistic regression with Bonferroni correction for multiple testing. Results: The risk allele in rs2239547 (ITIH3/4-region) was significantly associated with a history of suicide attempt (p ¼ 0.01) after multiple testing correction (p threshold o 0.017). The previous suicide attempt susceptibility loci were only nominally associated, but had the same direction of risk in the replication sample (sign test, p ¼ 0.02). Limitations: Relatively small sample size and retrospective clinical assessment. Conclusions: We detected a novel association between suicide attempt and the ITIH3/4-region in a combined group of patients with BD, SCZ and related psychosis spectrum disorders. This may be useful in understanding molecular mechanisms of suicidal behaviour in severe mental disorders, although replication is warranted. Keywords: Suicidal behaviour; Bipolar disorder; Schizophrenia; Candidate gene