A Gene-Environment Interaction Study of Polygenic Scores and Maltreatment on Childhood ADHD

Abstract

This study explored whether maltreatment moderates the association of polygenic risk for ADHD. Because individuals with low polygenic scores (PGS) for ADHD were previously shown to have better than expected functional outcomes (i.e., cognitive, mental health, social-emotional) than individuals with middle or high ADHD PGS, we hypothesized low ADHD PGS may confer a protective effect from maltreatment in the development of ADHD. Data were from participants with phenotypic and genotypic data in the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 4,722). ADHD PGS were generated from the most recent genome-wide association study on ADHD and categorized into three groups (i.e., low, medium, high) using empirically determined cut-points. A maltreatment factor score was derived from five forms of self-reported maltreatment experiences prior to age 18. ADHD PGS and maltreatment were positively associated with ADHD symptoms, as expected. However, no interaction between ADHD PGS and maltreatment on ADHD symptoms was detected. Despite the increase in predictive power afforded by PGS, the lack of an interaction between ADHD PGS and maltreatment on ADHD symptoms converges with an emerging body of PGS studies that have also failed to detect PGS-environment interplay in mental disorders. We discuss possible reasons for this pattern of results and offer alternative methods for future research in understanding gene-environment interactions.

Keywords: ADHD; Add Health; Gene-environment interaction; Maltreatment; Polygenic scores.