Exploring the association of interleukin polymorphisms with aggression and internalizing behaviors in children and adolescents.

Abstract

There is growing evidence that inflammation influences mental health. Blood interleukin levels, which regulate inflammation, have been linked to aggression and internalizing behaviors. We performed a hypothesis-driven genetic study to (1) evaluate the association of IL1B, IL2, and IL6 gene variants with aggression and internalizing behaviors and (2) explore gene-environment interactions with childhood adversity in a deeply phenotyped childhood-onset aggression sample including 255 cases and 226 controls of European ancestry. We evaluated the association of putative functional and tag SNPs within IL1B, IL2, and IL6 with aggression case status, parent-reported internalizing problems, self-reported anxiety symptoms, and self-reported depressive symptoms in our sample. We also performed exploratory GxE analyses within cases, testing for statistical interaction between interleukin SNP genotype and childhood adversity for depressive symptoms. No significant association was observed between any of the interleukin SNPs and childhood-onset aggression. We observed association of IL6 variant rs2069827 with depressive symptoms (p=7.15×10-4 ), and trends for an interaction between severe childhood adversity and SNPs in IL1B and IL2 for depressive symptoms. Our findings provide preliminary evidence that common variation in IL6 may be associated with depressive symptoms in children and adolescents, and that common variation in interleukin genes may sensitize individuals to the depressogenic effects of traumatic life experiences. Replication in independent samples is needed.