SU9 - IDENTIFICATION OF GENES IN CHILD GENETIC RISK FOR ATTENTION DEFICIT/HYPERACTIVITY DISORDER THAT INTERACT WITH MATERNAL DEPRESSIVE SYMPTOMS IN PREDICTION OF INTERNALIZING PROBLEMS

Abstract

Background Maternal antenatal depression is associated with offspring socio-emotional problems. However, the impact varies across the population such that some individuals seem resilient. Genetic factors may define vulnerability/resilience to the environment, effects that likely span many molecular pathways. Despite moderate success in candidate gene approaches, genome-wide approaches in gene-environment interactions (GxE) have been under exploited. We sought to identify genes and biological pathways that moderate the relationship between Maternal Antenatal Depressive Symptoms (MADS) and child socio-emotional outcomes. Methods Our sample included 190 mother-child dyads from a Canadian longitudinal birth cohort. MADS was measured with the Center for Epidemiologic Studies – Depression Scale. Child socio-emotional outcomes were mother-reported at 5 years with the Child Behavior Checklist. We constructed Genomic Profile Risk Scores (GPRS) from the children's SNPs genome-wide that account for polygenic risk for Attention Deficit/Hyperactivity Disorder (ADHD) based on risk information from the genome-wide associations with ADHD by the Psychiatric Genomics Consortium and applied them in our GxE model. GPRS with the smallest p-value in the GxE model was defined as the best-fit GPRS. SNPs constituting the best-fit GPRS were used in a genome-wide by environment association analysis follow-up. We used MetaCore to examine the enriched gene ontology in a subset of SNPs in the GxE model with p-values less than .01. Results GPRS moderated the relationship between MADS and child internalizing problems (p Discussion We used the GPRS for ADHD to facilitate our genome-wide approach in examining GxE and identified genes that have a moderating effect on the relationship between MADS and internalizing problems in children. The enriched biological pathways are implicated in axon development and synaptic functions, critically important in fetal neurodevelopment. These findings suggest that specific genes involved in the biological framework for antenatal neurodevelopment can confer sensitivity or resilience to the influences of MADS on mental health.