Genetic variations in the serotoninergic system and environmental factors contribute to aggressive behavior in Chinese adolescents

• With 478 healthy Chinese, we found that 12 serotonin-related SNPs were associated with aggression.
• HTR2C interacts with HTR5A as well as stressful life event on aggression.
• Gene, environment and their interactions together accounted for 1/5 of aggression variation.

Aggressive behavior is a major public health problem worldwide and has been associated with many gene variants, especially those related to the serotonin (5-hydroxytryptamine, 5-HT) system, and environmental factors. However, the overall contribution of serotonin-related genes to aggressive behavior is not well understood. With a sample of 478 healthy Chinese volunteers, this study investigated the relation between aggressive behavior and genetic variations of the serotoninergic system (as characterized by 129 representative polymorphisms) interacting with environmental factors (parental warmth and acceptance; stressful life events). We adopted a system-level approach to identify SNPs and environmental factors associated with aggressive behavior, and estimated their overall contribution to aggressive behavior using multiple regression, which was then verified by permutation analysis. We identified 12 SNPs that made statistically significant contributions to aggressive behavior. Next, main effects, interactions among these SNPs, and interactions between these SNPs and environmental factors were assessed using multiple regression. The final model accounted for approximately 19% of the variance for aggressive behavior. Permutation analysis confirmed that the probability of obtaining these findings by chance was low (p = 0.045, permuted for 1000 times). These results showed that genetic variations in the serotoninergic system, combined with environmental risk factors, made a moderate contribution to individual differences in aggressive behavior among a healthy population sample.