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Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Netherlands Institute for the Study of Crime and Law Enforcement, Amsterdam, the Netherlands; Department of Methodology and Statistics, Universiteit Utrecht, Utrecht, the Netherlands.
Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0002-6851-3297
Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain; Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona (UB), Barcelona, Spain.
Number of Authors: 1292025 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 57, no 10, p. 2427-2435Article in journal (Refereed) Published
Abstract [en]

We performed a genome-wide association meta-analysis (GWAMA) of 290,134 attention-deficit/hyperactivity disorder (ADHD) symptom measures of 70,953 unique individuals from multiple raters, ages and instruments (ADHDSYMP). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHDOVERALL). ADHDSYMP returned no genome-wide significant variants. We show that the combined ADHDOVERALL GWAMA identified 39 independent loci, of which 17 were new. Using a recently developed gene-mapping method, Fine-mapped Locus Assessment Model of Effector genes, we identified 22 potential ADHD effector genes implicating several new biological processes and pathways. Moderate negative genetic correlations (rg < -0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHDOVERALL outperformed PGSs based on ADHD symptoms and diagnosis alone. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts helps to identify new genes implicated in ADHD.

Place, publisher, year, edition, pages
Nature Publishing Group, 2025. Vol. 57, no 10, p. 2427-2435
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-123776DOI: 10.1038/s41588-025-02295-yISI: 001688603500002PubMedID: 40962958Scopus ID: 2-s2.0-105016606413OAI: oai:DiVA.org:oru-123776DiVA, id: diva2:1998850
Funder
EU, FP7, Seventh Framework Programme, 602768
Note

Erratum: van der Laan, C.M., Ip, H.F., Schipper, M. et al. Publisher Correction: Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes. Nat Genet (2025). https://doi.org/10.1038/s41588-025-02383-z

Available from: 2025-09-18 Created: 2025-09-18 Last updated: 2026-02-26Bibliographically approved

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