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Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.
Nat. Genet. 57, 2427-2435 (2025)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Sprache
englisch
Veröffentlichungsjahr
2025
HGF-Berichtsjahr
2025
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Zeitschrift
Nature Genetics
Quellenangaben
Band: 57,
Heft: 10,
Seiten: 2427-2435
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504000-008
Scopus ID
105016606413
PubMed ID
40962958
Erfassungsdatum
2025-10-21