Influence of differentially expressed genes from suicide post-mortem study on personality traits as endophenotypes on healthy subjects and suicide attempters.
Although a genetic contribution to the complex aetiology of suicidal behaviour has been suggested since many years, the attempt to identify specific genes related to suicide has led to contrasting results. In a post-mortem study on suicide, we previously detected several differentially expressed genes which, however, have not been subsequently associated with suicidal behaviour, or only nominally. Therefore, personality traits may represent good intermediate endophenotypes. Our primary aim was to investigate the potential modulation of several single-nucleotide polymorphisms (SNPs) of the same previously investigated genes (S100A13, EFEMP1, PCDHB5, PDGFRB, CDCA7L, SCN2B, PTPRR, MLC1 and ZFP36) on personality traits, as measured with the Temperament and Character Inventory (TCI), in a German sample composed of 287 healthy subjects (males: 123, 42.9 %; mean age: 45.2 ± 14.9 years) and in 111 psychiatric patients who attempted suicide (males: 43, 38.6 %; mean age: 39.2 ± 13.6 years). Multivariate analysis of covariance was used to test possible influence of single SNPs on TCI scores. Genotypic, allelic and haplotypic analyses have been performed. Controlling for sex, age and educational level, genotypic analyses showed a modulation of EFEMP1 rs960993 and rs2903838 polymorphisms on both harm avoidance and self-directedness in healthy subjects. Interestingly, we could replicate these associations in haploblocks within controls (p < 0.0001) and in the independent sample of suicide attempters for harm avoidance (p < 0.00001), a phenotype highly associated with suicidal behaviour. This study suggests that EFEMP1 SNPs, never investigated in association with suicidal behaviour and related personality, could be involved in its modulation in healthy subjects as well as in suicide attempters.