52: COMMON GENETIC RISK VARIANTS FOR ADHD CONTRIBUTE TO CHILDHOOD NEURODEVELOPMENTAL AND EXTERNALIZING TRAITS IN THE POPULATION

Abstract

Background ADHD is a highly heritable disorder, marked by elevated levels of 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 neurodevelopmental and externalizing traits associated with ADHD. Methods ADHD PRS were calculated using results from the latest iPSYCH/Psychiatric Genomics Consortium ADHD Genome-Wide Association (GWAS) meta-analysis for 13,471 children from the Child and Adolescent Twin Study in Sweden (CATSS). For replication, ADHD PRS were also calculated from the EAGLE consortia GWAS meta-analyses of ADHD traits. Phenotypes in CATSS were measured via parent-ratings using the Autism-Tics, ADHD, and Other Comorbidities inventory. To estimate the associations between ADHD PRS and neurodevelopmental and externalizing traits, we used confirmatory factor analysis to fit a correlated factors model to the symptoms of trait inattention, impulsivity, autism, learning difficulties, oppositional-defiant and conduct problems. Each latent trait factor was then regressed on ADHD PRS in a structural equation modelling framework. In the second model, we included a latent general psychopathology factor to account for phenotypic associations among the traits. In this model, each item loaded on the latent general factor, in addition to the corresponding latent trait factor described above. Analyses were re-run using the EAGLE ADHD PRS. Results 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 latent general psychopathology factor, on which all symptoms loaded positively (loadings=.31–.91, S.E.=.004–.028). ADHD PRS explained 1% (β =.10, p Discussion Our results suggest that common genetic variants associated with clinically diagnosed ADHD have pleiotropic effects on neurodevelopmental and externalizing traits in the general population. These associations appear to be largely non-specific and reflect a general liability towards elevated childhood neurodevelopmental traits. Nonetheless, over and above predicting a general psychopathology factor, the ADHD PRS also seemed to capture genetic risk variants with unique effects on childhood externalizing traits of impulsivity and conduct problems.