Association and CpG SNP analysis of HTR4 polymorphisms with suicidal behavior in subjects with schizophrenia

Suicide is a major contributor to the morbidity and mortality rates in schizophrenia. Genetic and epigenetic factors have been reported to modulate the risk for suicide although the precise mechanism and magnitude of these contributions is unknown. Previous research indicates that suicide attempters present abnormalities in the serotonergic system. The present study aimed to identify genetic and epigenetic risk variants of the serotonin 5-HT₄ receptor gene (HTR4) for suicidal behavior. We included 234 subjects diagnosed with schizophrenia. For this purpose, we analyzed 11 markers across HTR4 and performed genotype, haplotype and potential methylation analyses, correcting for clinical covariates and ethnic stratification. Three blocks were revealed from the LD analysis. Haplotypes in Block 3 were significantly associated with suicide attempt. The potential methylation analysis was not significant. Our results suggest that HTR4 polymorphisms may not play a major role in the susceptibility for suicidal behavior in subjects with schizophrenia. Moreover, although not significant, the CpG SNP potential methylation analysis would be informative for future methylation analysis on this gene.