Background Common genetic variants make a significant contribution to dimensional neurodevelopmental characteristics such as ADHD symptoms and cognitive abilities. The relevance and structure of these associations within a transdiagnostic sample referred for difficulties in cognition, attention and learning has not been demonstrated. Methods Polygenic scores (PGS) derived from recent genome-wide association study (GWAS) data on ADHD and Intelligence were calculated from genome-wide genotyping data 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 neurodevelopmental characteristics, and factor scores from a hierarchical model of psychopathology. Associations were explored with and without co-varying for socio-economic status (SES). Results We found the expected associations within the sample between ADHD-PGS and ADHD symptom dimensions, and between Intelligence-PGS and IQ test scores. ADHD-PGS were also associated with broader externalising behaviours and with verbal intelligence, but the latter only if SES was not included as a covariate. Examining associations with hierarchical factor scores, we found a relationship between ADHD-PGS and a general mental health factor, externalising factor, and social maladjustment factor, however these associations did not survive co-variation for SES and correction for multiple comparisons. The Intelligence-PGS showed significant associations only with verbal and non-verbal cognitive skills, which were independent of SES; and no links were observed with ADHD traits or mental health factor scores. Conclusion Our finding suggest that PGS derived from previous GWAS have research utility for paediatric transdiagnostic samples, showing both specific and general associations with neurodevelopmental traits. Future studies investigating PGS and cognitive and neural correlates within this cohort, as well as gene-by-environment interactions, may contribute to our understanding of developmental pathways and risk-resilience mechanisms in child mental health.

The authors have declared no competing interest.

Medical Research Council (G116768) Isaac Newton Trust Wellcome Trust ISSF University of Cambridge Joint Research Grants scheme National Institute for Health and Care Research Cambridge Biomedical Research Centre (NIHR203312) and the NIHR Applied Research Collaboration East of England EU Horizon2020 (Grant agreement number: 732592)

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All procedures complied with the ethical standards of the national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving human participants were approved by the National Health Service, Health Research Authority NRES Committee East of England (REC: 13/EE/0157, IRAS 127675).

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Behavioural and cognitive data is available online through the CALM Managed Open Access repository: https://portal.ide-cam.org.uk/overview/1158. Genetic data is available via collaboration with CALM.

https://portal.ide-cam.org.uk/overview/1158