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van der Laan, C.M.* ; Ip, H.F.* ; Schipper, M.* ; Hottenga, J.J.* ; St Pourcain, B.* ; Zayats, T.* ; Pool, R.* ; Krapohl, E.M.L.* ; Brikell, I.* ; Soler Artigas, M.* ; Cabana-Domínguez, J.* ; Nolte, I.M.* ; Bolhuis, K.* ; Palviainen, T.* ; Zafarmand, H.* ; Gordon, S.* ; Aliev, F.* ; Burt, S.A.* ; Wang, C.A.* ; Saunders, G.* ; Karhunen, V.* ; Adkins, D.E.* ; Border, R.* ; Peterson, R.E.* ; Prinz, J.A.* ; Thiering, E. ; Vilor-Tejedor, N.* ; Ahluwalia, T.S.* ; Allegrini, A.G.* ; Rimfeld, K.* ; Chen, Q.* ; Lu, Y.* ; Martin, J.* ; Bosch, R.* ; Ramos-Quiroga, J.A.* ; Neumann, A.* ; Ensink, J.* ; Grasby, K.L.* ; Morosoli, J.J.* ; Tong, X.* ; Marrington, S.* ; Scott, J.G.* ; Shabalin, A.A.* ; Corley, R.* ; Evans, L.M.* ; Sugden, K.* ; Alemany, S.* ; Sass, L.* ; Vinding, R.* ; Ehli, E.A.* ; Hagenbeek, F.A.* ; Derks, E.M.* ; Larsson, H.* ; Snieder, H.* ; Cecil, C.* ; Whipp, A.M.* ; Korhonen, T.* ; Vuoksimaa, E.* ; Rose, R.J.* ; Uitterlinden, A.G.* ; Haavik, J.* ; Harris, J.R.* ; Helgeland, Ø.* ; Johansson, S.* ; Knudsen, G.P.S.* ; Njolstad, P.R.* ; Lu, Q.* ; Rodriguez, A.* ; Henders, A.K.* ; Mamun, A.* ; Najman, J.M.* ; Brown, S.* ; Hopfer, C.* ; Krauter, K.* ; Reynolds, C.A.* ; Smolen, A.* ; Stallings, M.C.* ; Wadsworth, S.* ; Wall, T.L.* ; Eaves, L.J.* ; Silberg, J.L.* ; Miller, A.* ; Havdahl, A.* ; Llop, S.* ; Lopez-Espinosa, M.J.* ; Bønnelykke, K.* ; Sunyer, J.* ; Arseneault, L.* ; Standl, M. ; Heinrich, J. ; Boden, J.M.* ; Pearson, J.* ; Horwood, J.* ; Kennedy, M.* ; Poulton, R.* ; Maes, H.H.* ; Hewitt, J.K.* ; Copeland, W.E.* ; Middeldorp, C.M.* ; Williams, G.M.* ; Wray, N.R.* ; Järvelin, M.R.* ; McGue, M.* ; Iacono, W.G.* ; Caspi, A.* ; Moffitt, T.E.* ; Whitehouse, A.J.O.* ; Pennell, C.E.* ; Klump, K.L.* ; Jiang, C.* ; Dick, D.M.* ; Reichborn-Kjennerud, T.* ; Martin, N.G.* ; Medland, S.E.* ; Vrijkotte, T.* ; Kaprio, J.* ; Tiemeier, H.* ; Davey Smith, G.* ; Hartman, C.A.* ; Oldehinkel, A.J.* ; Casas, M.* ; Ribasés, M.* ; Lichtenstein, P.* ; Lundstrom, S.* ; Plomin, R.* ; Bartels, M.* ; Nivard, M.G.* ; Boomsma, D.I.* ; Llonga, N.*

Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.

Nat. Genet. 57, 2427-2435 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 57, Issue: 10, Pages: 2427-2435 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504000-008
DOI 10.1038/s41588-025-02295-y
Scopus ID 105016606413
PubMed ID 40962958
Erfassungsdatum 2025-10-21
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