HLA Class II Alleles and Suicidal Behavior: Evidence from a Case–Control Study

TL;DR

This study finds that certain HLA gene variants are linked to an increased risk of suicidal behavior, suggesting a genetic component to suicide susceptibility.

Contribution

The study identifies specific HLA-DQB1 and HLA-DRB1 alleles associated with suicidal behavior, providing novel genetic insights into suicide risk.

Findings

HLA-DQB1*02/06 and HLA-DRB1*11/15 genotypes are linked to increased suicidal behavior risk.

The HLA-DRB1*15~DQB1*03 haplotype is associated with higher suicide risk.

Psychosocial factors like bereavement and memory dysfunction correlate with specific HLA alleles.

Abstract

Suicidality is a complex multifactorial phenomenon strongly associated with major depression and other psychiatric disorders. Building on evidence implicating the Major Histocompatibility Complex (MHC) in modulating the immune and inflammatory processes characterizing psychiatric disorders, we hypothesized that specific HLA-DQB1 and HLA-DRB1 variants may contribute to an increased genetic susceptibility to suicidal behavior. Human Leucocyte Antigen (HLA) typing by sequence-specific primers (PCR-SSP) was performed on a sample of 196 individuals, including 70 non-lethal suicide attempters, 28 cases of completed suicide, and matched controls. The *HLA-DQB1 02/06 (RR 1.60, CI95% 1.22–2.09, p = 0.03 *) and *HLA-DRB1 11/15 (RR 1.70, CI95% 1.3–2.24, p = 0.04 *) genotypes and the HLA-DRB115~DQB103 haplotype (RR 1.58, CI95% 1.22–2.04, p = 0.03 *) were found to favor suicidal behavior. Psychosocial determinants associated with an increased suicidal risk were bereavement of close relatives (linked with HLA-DQB1*02), memory dysfunction (HLA-DQB1*06), disillusionment (HLA-DRB1*07 and HLA-DRB1*15), and self-harm (HLA-DRB1*15). Our findings support the contributory role of HLA polymorphisms in shaping susceptibility to suicidal behavior.