ADHD and Intelligence polygenic scores and their associations with dimensional developmental characteristics within a paediatric transdiagnostic cohort
Authors: Santangelo Andrea M. , Ohlei Olena , Mareva Silvana , Brkic Diandra ,   CALM team, Bertram Lars , Holmes Joni , Astle Duncan , Baker Kate 
Published: December 2023

AbstractBackgroundCommon 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.MethodsPolygenic 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).ResultsWe 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.ConclusionOur 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.Key pointsCommon polygenic variation, quantified by PolyGenic Scores (PGS), contributes to dimensional neurodevelopmental characteristics. However, PGS relevance has not been demonstrated in a paediatric transdiagnostic sample.We studied the associations between neurodevelopmental dimensions and ADHD PGS or Intelligence PGS, within a cohort of children referred for difficulties in cognition, attention and/or learning.ADHD-PGS contributed to ADHD symptoms, as well as to externalizing behaviours, verbal intelligence, and hierarchical factors of mental health, with some of these associations being influenced by socioeconomic status (SES).Intelligence-PGS in contrast, showed associations only with cognitive skills (verbal and non-verbal IQ), which were independent of SES; and did not link with ADHD traits or mental health factor scores.Further research building on these findings will contribute to our understanding of developmental pathways and risk-resilience mechanisms in child mental health.