ADHD and Intelligence polygenic scores and their associations with dimensional developmental characteristics within a paediatric transdiagnostic cohort

Common genetic variants make a significant contribution to neurodevelopmental characteristics such as cognitive abilities and ADHD symptoms. The relevance and structure of these associations amongst children with transdiagnostic difficulties in cognition, attention and learning has not been explored. Polygenic scores (PGS) derived from the largest genome-wide association study (GWAS) data at the time of this study on ADHD (38,691 individuals with ADHD and 186,843 controls) and Intelligence (269,867 individuals) were calculated for 524 children and young people (5-18 years old) referred to the Centre for Attention, Learning and Memory (CALM). PGS-trait associations were assessed via linear regression analyses, for a range of cognitive and behavioural dimensional measures, and factor scores from a hierarchical model of psychopathology. PGS associations were explored with and without co-varying for socio-economic status (SES). Within this sample, we found the expected positive associations between ADHD-PGS and ADHD primary symptoms, and between Intelligence-PGS and IQ. ADHD-PGS were also associated with broader externalising behaviours and intelligence scores, and these associations remained significant after removing ADHD-diagnosed participants, or after covarying with SES. Intelligence-PGS showed associations with verbal and non-verbal cognitive skills, but no significant associations with ADHD traits were detected. For the hierarchical model of psychopathology, ADHD-PGS, but not intelligence-PGS, showed associations with the general mental health factor, externalising factor, and social maladjustment factor, only when SES was not included as a covariate. In summary, PGS for neurodevelopmental traits may contribute to both general and specific cognitive and behavioural dimensions in a paediatric transdiagnostic sample. Future studies investigating PGS associations with neural correlates, as well as gene-by-environment interactions, will contribute to our understanding of developmental pathways and risk-resilience mechanisms in child mental health.