A case-control association study of 12 candidate genes and attempted suicide in French adolescents

Abstract

Background Suicide is the second leading cause of death for 10-19-year-olds. Evidence has shown that attempted suicide is a complex interplay of genes and environmental factors. In the adult population, possible associations between genetic polymorphisms and suicidal behaviors have been investigated for several genes, most often with inconsistent findings and poor replicability of significant associations. This study aimed to identify gene variants conferring risk for adolescent suicide attempt. Methods We selected the genes and variants after an analysis of the literature and a selection of the most significant associations identified. We performed analysis on 22 single nucleotide polymorphisms (SNPs) in 12 genes (COMT, CRHR1, FKBP5, SLC6A4, HTR1B, HTR2A, TPH1, TPH2, BDNF, NTRK2, NOS1 and IL28RA) for association with suicide attempt, hopelessness and impulsivity in an independent sample, composed of 98 adolescent suicide attempters who required hospitalization based on emergency assessments, and 150 healthy volunteers. Quality controls, deviations from the Hardy-Weinberg disequilibrium and statistical tests of association (case/control) were calculated using PLINK. Asymptotic p-values were corrected with the Benjamini-Hochberg method. The level of significance was set to 0.05. Results We identified four polymorphisms of interest, rs10868235 (NTRK2), rs1659400 (NTRK2), rs2682826 (NOS1) and rs7305115 (TPH2), with significant associations for suicide attempts or for the quantitative hopelessness or impulsivity phenotypes. However, none of the associations withstand statistical correction tests. Conclusion Our results do not support the role of the 22 SNPs selected in suicide attempt or hopelessness and impulsivity in adolescent population. However, the relatively small sample size and the probable effect of gene-gene interaction or gene-environment interaction on suicidal behavior could not be ruled out.

Keywords: SNPs; adolescent; attempt suicide; genetic association; polymorphisms.