ADHD and intelligence polygenic scores associations with developmental dimensions in children with attention, learning and memory difficulties

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 demonstrated. Polygenic scores (PGS) derived from genome-wide association study (GWAS) data on ADHD and Intelligence were calculated for 524 children and young people referred to the Centre for Attention, Learning and Memory (CALM). PGS-trait associations were tested via linear regression analyses, for a range of cognitive and behavioural 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. Whilst ADHD-PGS were also associated with broader externalising behaviours and intelligence scores, intelligence-PGS showed associations only with verbal and non-verbal cognitive skills, and not with ADHD traits. These associations remained significant after removing ADHD-diagnosed participants, or after covarying with SES. 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 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.