Investigating the role of BDNF and CCK system genes in suicidality in a familial bipolar cohort

BackgroundSuicidal behaviour is a phenotype widely associated with psychiatric disorders such as major depressive disorder and bipolar disorder. However, recent evidence indicates that part of the heritability of suicidal behaviour is independent of the heritability of individual psychiatric disorders. This allows investigation into genetic risk factors for suicidal behaviour within a disorder using a candidate gene association approach.MethodsWe used family-based association testing in a cohort of 130 multiplex bipolar pedigrees, comprising 795 individuals, to look for associations between suicidal behaviour and 32 single nucleotide polymorphisms (SNPs) from across the genes brain-derived neurotrophic factor (BDNF), cholecystokinin (CCK) and the cholecystokinin beta-receptor (CCKBR).ResultsWe found associations (p≤0.05) between suicide attempt and 12 SNPs of CCKBR and five SNPs of BDNF. After correction for multiple testing, seven SNPs of CCKBR remained significantly associated. No association was found between CCK and suicidal behaviour.LimitationsThe study relied on retrospective self-reporting by individuals to determine phenotype, and the sample size was relatively small.ConclusionsThe results of the study support the hypothesis that some CCKBR polymorphisms may contribute to an underlying predisposition towards suicidal behaviour in bipolar disorder.