The Moderating Effect of the Ankyrin Repeat and Kinase Domain Containing One Gene on the Association of Family Environment with Longitudinal Executive Function following Traumatic Brain Injury in Early Childhood: A Preliminary Study

Abstract

This study examined whether the ankyrin repeat and kinase domain containing 1 gene (ANKK1) C/T single-nucleotide polymorphism (SNP) rs1800497 moderated the association of family environment with long-term executive function (EF) following traumatic injury in early childhood. Caregivers of children with traumatic brain injury (TBI) and children with orthopedic injury completed the Behavior Rating Inventory of Executive Function (BRIEF) at post-injury visits. DNA was collected to identify the rs1800497 genotype in the ANKK1 gene. General linear models examined gene-environment interactions as moderators of the effects of TBI on EF at two times post-injury (12 months and 7 years). At 12 months post-injury, analyses revealed a significant three-way interaction of genotype with level of permissive parenting and injury type. Post hoc analyses showed genetic effects were more pronounced for children with TBI from more positive family environments, such that children with TBI who were carriers of the risk allele (T-allele) had significantly poorer EF compared with non-carriers only when they were from more advantaged environments. At 7 years post-injury, analyses revealed a significant two-way interaction of genotype with level of authoritarian parenting. Post hoc analyses found that carriers of the risk allele had significantly poorer EF compared with non-carriers only when they were from more advantaged environments. These results suggest a gene-environment interaction involving the ANKK1 gene as a predictor of EF in a pediatric injury population. The findings highlight the importance of considering environmental influences in future genetic studies on recovery following TBI and other traumatic injuries in childhood.