Risk for intentional violent death associated with HLA genotypes: a preliminary survey of deceased American organ donors

Abstract

This study investigates the different Human Leukocyte Antigen (HLA) genotypes and their possible associations with both disease and behavior, specifically by describing significant associations between particular HLA genotypes and occurrence of intentional violent death. A de-identified dataset of n = 216,426 deceased American organ donors was analyzed for all possible genotypes by comparing the Independent Variable (Each specific HLA genotype vs. remainder of sample, non-genotype) on the Dependent Variable (Intentional Violent vs. Non-violent death). For HLA-A, 17 heterozygotes were significantly associated with increased occurrence of intentional violent death, with heightened prevalence for HLA-A2, HLA-A23, HLA-A30, HLA-A68, and HLA-A74 alleles. For HLA-B, 32 heterozygotes were significant, 25 of which (e.g., HLA-B7, HLA-B8, HLA-B35, HLA-B44, and HLA-B53) exhibited heightened prevalence of violent death. For HLA-BW, homozygotes had significantly increased odds ratios for intentional violent death. For HLA-DRB1, 19 heterozygotes were significant, with heightened prevalence only for the HLA-DRB1-4 allele. There were no racial differences in risk for the significant HLA-A and HLA-B genotypes. These exploratory, not necessarily causal, results provide the first indications of possible HLA-aggression associations in humans, supporting animal models.

Association of HLA class II alleles with suicidal behavior in a Transylvanian population

“…In accordance with these data, a Tunisian study found the DQB1*02 allele to be the most susceptible and DQB1*05 the most protective in schizophrenia patients [32]. On the other hand, an American study on a huge cohort of mainly Caucasian deceased organ donors [33] which associated intentional violent death with 21 HLA-DR and 10 HLA-DQ alleles found both DQB1*02 and DQB1*05 to be significantly associated with increased risks for violent death.…”

The Influence of HLA Alleles on the Affective Distress Profile

“…Over the years, there have been numerous studies on the associations between different HLA alleles and infectious or immune diseases [7][8][9][10][11], but few studies have tried to find associations between HLA genotypes and different behaviors or mental states. For example, associations were found between HLA alleles and suicidal behavior [12,13], between HLA genotypes and aggression [14], and between the HLA system and psychosis [15] or panic disorder [16].…”