ADHD and intelligence polygenic scores associations with developmental dimensions in children with attention, learning and memory difficulties
9 affiliations
- 1MRC Cognitive and Brain Sciences Unit, University of Cambridge, Cambridge, UK
- 2MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- 3Lubeck Interdisciplinary Platform for Genome Analysis, University of Luebeck, Luebeck, Germany
- 4Psychology Department, University of Exeter, Exeter, UK
- 5Brain Health Department, Nestlé Institute of Health Sciences, Lausanne, Switzerland
- 6School of Psychology, University of East Anglia, Norwich, UK
- 7Department of Psychiatry, University of Cambridge, Cambridge, UK
- 8Department of Genomic Medicine, University of Cambridge, Cambridge, UK
- 9Department of Pathology, University of Cambridge, Cambridge, UK
Abstract
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.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00787-026-03086-4.
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BibTeX
@article{santangelo2026adhd,
title = {{ADHD and intelligence polygenic scores associations with developmental dimensions in children with attention, learning and memory difficulties}},
author = {Andrea M. Santangelo and Olena Ohlei and Silvana Mareva and Diandra Brkic and CALM team and Lars Bertram and Joni Holmes and Duncan Astle and Kate Baker},
journal = {European Child \& Adolescent Psychiatry},
year = {2026},
month = jun,
doi = {10.1007/s00787-026-03086-4},
url = {https://doi.org/10.1007/s00787-026-03086-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ADHD and intelligence polygenic scores associations with developmental dimensions in children with attention, learning and memory difficulties
AU - Andrea M. Santangelo
AU - Olena Ohlei
AU - Silvana Mareva
AU - Diandra Brkic
AU - CALM team
AU - Lars Bertram
AU - Joni Holmes
AU - Duncan Astle
AU - Kate Baker
PY - 2026
DA - 2026/06/13
JO - European Child & Adolescent Psychiatry
DO - 10.1007/s00787-026-03086-4
UR - https://doi.org/10.1007/s00787-026-03086-4
AB - 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. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00787-026-03086-4.
SN - 1018-8827
SN - 1435-165X
ER -