A Combined Impact of Neurotransmitter System Genes and Social/Lifestyle Factors on Aggressive Behavior

The development of human aggressive behavior is attributed to a combined effect of social/environmental factors and multiple genes of small effect. Molecular mechanisms have emphasized alterations in serotonin, dopamine, and norepinephrine signaling could contribute to various behavioral traits, including aggression. Therefore, the present study aimed to examine a contribution of multiple genetic variants belonging to neurotransmitter system genes together with social/lifestyle factors in individual differences in aggression level in the cohort of young adults from Russia. In addition, we sought to determine the common and specific patterns of genetic associations between different aggression subscales, i.e., physical and verbal aggression, anger, and hostility. The study examined mentally healthy young adults from Russia aged 18–25 years (N = 1307, 80% women), who underwent psychological testing using the Buss-Perry Aggression Questionnaire (BPAQ) and the Parental-Bonding Inventory (PBI). Genotyping was performed on 32 SNPs located in the HTR1B, HTR2A, HTR3A, HTR3B, TH, TPH1, TPH2, DDC, DRD1, DRD2, SLC6A2, SLC6A3, ADRB2, and COMT genes. Statistical analysis enabled to determine common and specific patterns of genetic associations of the HTR1B rs13212041, HTR2A rs7997012, HTR3A rs11604247 and rs1176722, TPH2 rs1843809, DRD2 rs12364283, DDC rs921451, SLC6A2 rs2242446 and rs3785143, and COMT rs4646316 with individual variance in the total aggression and its subscales. The most significant regression models, which included SNPs and social predictors, enabled to explain up to 12.1% of differences in the total aggression score (p = 1.3 × 10–10), 11.3% in anger (p = 2.2 × 10–16), 9.7% in verbal aggression (p = 8.0 × 10–10), and 4.1% in hostility (p = 1.2 × 10–8). The data obtained evidence a relation of allelic variants linked to upregulation of the HTR3A and SLC6A2 genes and downregulation of the HTR1B, HTR2A, TPH2, DRD2, and COMT genes to higher aggression levels.