ADHD is a highly heritable disorder, marked by comorbidity across neurodevelopmental and externalizing conditions. Polygenic risk scores (PRS) for ADHD have previously been shown to predict ADHD clinical case status and ADHD traits in the general population (Martin, Hamshere, Stergiakouli, O'Donovan, & Thapar, 2014; Stergiakouli et al., 2015). However, it is still unknown to what extent these genetic risk variants are disorder specific, and how they may influence related neurodevelopmental and externalizing traits.
We calculated ADHD PRS for 13,471 children from the Child and Adolescent Twin Study in Sweden, using results from the latest iPSYCH/Psychiatric Genomics Consortium ADHD genome-wide association (GWAS) meta-analysis. We used confirmatory factor analysis and structural equation modelling to estimate the associations between ADHD PRS and neurodevelopmental and externalizing traits, whilst accounting for covariance across traits.
ADHD PRS were significantly associated with elevated levels of trait inattention, impulsivity, autism, learning difficulties, oppositional-defiant and conduct problems. However, only unique associations with impulsivity and conduct problems remained after accounting for cross-trait covariance via a general latent factor, on which all symptoms loaded positively (loadings=.31-.91, S.D=.004-.028). ADHD PRS explained 0.01% (β =.10, p < 0.000) of the variance in the latent general factor, 0.005% (β =.073, p < 0.000) in impulsivity and 0.003% (β =.052, p =.035) in conduct problems. We replicated these findings using ADHD PRS based on a GWAS of population ADHD traits.
Our results suggest that common genetic variants associated with clinically diagnosed ADHD have pleiotropic effects on neurodevelopmental and externalizing traits in the general population, which indicate that these associations appear to be largely non-specific. Nonetheless, the ADHD PRS does not only reflect a general liability to childhood neurodevelopmental traits, but also seem to capture genetic risk variants with unique effects on externalizing traits.
Developmental Disorders (e.g. ADHD)
