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

March 9, 2026

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

Publicated to: NATURE GENETICS. 57 (10): 2427-+ - 2025-10-01 57(10), DOI: 10.1038/s41588-025-02295-y

Authors:

van der Laan, CM; Ip, HF; Schipper, M; Hottenga, JJ; St Pourcain, B; Zayats, T; Pool, R; Krapohl, EML; Brikell, I; Artigas, MS; Cabana-Domínguez, J; Llonga, N; Nolte, IM; Bolhuis, K; Palviainen, T; Zafarmand, H; Gordon, S; Aliev, F; Burt, SA; Wang, CA; Saunders, G; Karhunen, V; Adkins, DE; Border, R; Peterson, RE; Prinz, JA; Thiering, E; Vilor-Tejedor, N; Ahluwalia, TS; Allegrini, A; Rimfeld, K; Chen, Q; Lu, Y; Martin, J; Bosch, R; Ramos-Quiroga, JA; Neumann, A; Ensink, J; Grasby, KL; Morosoli, JJ; Tong, XR; Marrington, S; Scott, JG; Shabalin, AA; Corley, R; Evans, LM; Sugden, K; Alemany, S; Sass, L; Vinding, R; Ehli, EA; Hagenbeek, FA; Derks, EM; Larsson, H; Snieder, H; Cecil, C; Whipp, AM; Korhonen, T; Vuoksimaa, E; Rose, RJ; Uitterlinden, AG; Haavik, J; Harris, JR; Helgeland, O; Johansson, S; Knudsen, GPS; Njolstad, PR; Lu, Q; Rodriguez, A; Henders, AK; Mamun, A; Najman, JM; Brown, S; Hopfer, C; Krauter, K; Reynolds, CA; Smolen, A; Stallings, M; Wadsworth, S; Wall, TL; Eaves, L; Silberg, JL; Miller, A; Havdahl, A; Llop, S; Lopez-Espinosa, MJ; Bonnelykke, K; Sunyer, J; Arseneault, L; Standl, M; Heinrich, J; Boden, J; Pearson, J; Horwood, J; Kennedy, M; Poulton, R; Maes, HH; Hewitt, J; Copeland, WE; Middeldorp, CM; Williams, GM; Wray, N; Järvelin, MR; McGue, M; Iacono, W; Caspi, A; Moffitt, TE; Whitehouse, AJO; Pennell, CE; Klump, KL; Jiang, C; Dick, DM; Reichborn-Kjennerud, T; Martin, NG; Medland, SE; Vrijkotte, T; Kaprio, J; Tiemeier, H; Smith, GD; Hartman, CA; Oldehinkel, AJ; Casas, M; Ribasés, M; Lichtenstein, P; Lundström, S; Plomin, R; Bartels, M; Nivard, MG; Boomsma, DI

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Affiliations

Acad Ctr Child & Adolescent Psychiat, Levvel - Author

Amsterdam Publ Hlth Res Inst - Author

Amsterdam Reprod & Dev Res Inst - Author

Arkin Mental Hlth Care - Author

Avera McKennan Hosp - Author

Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res - Author

Brunel Univ London, Dept Life Sci, Coll Hlth & Life Sci - Author

CIBER Epidemiol & Salud Publ CIBERESP - Author

Duke Univ, Ctr Genom & Computat Biol - Author

Duke Univ, Dept Psychol & Neurosci - Author

Duke Univ, Sch Med, Dept Psychiat & Behav Sci - Author

Erasmus MC, Dept Child & Adolescent Psychiat Psychol - Author

Erasmus Univ, Med Ctr, Dept Epidemiol - Author

German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol - Author

Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci - Author

Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC - Author

Hosp St Joan Deu, Inst Recerca St Joan Deu, SJD MIND Sch Program - Author

Hunter Med Res Inst, Newcastle - Author

Indiana Univ, Dept Psychol & Brain Sci - Author

Inst Desarrollo Terapias Avanzadas Neurociencias - Author

Karolinska Inst, Dept Med Epidemiol & Biostat - Author

Kings Coll London, Inst Psychiat Psychol & Neurosci - Author

Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci - Author

Lovisenberg Diaconal Hosp, Nic Waals Inst - Author

Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Div Metab Dis & Nutr Med - Author

Michigan State Univ, Dept Psychol - Author

Natl Univ Singapore, Dept Psychol Med - Author

Netherlands Genom Initiat - Author

Norwegian Inst Publ Hlth, Ctr Fertil & Hlth - Author

Norwegian Inst Publ Hlth, Div Hlth Data & Digitalizat, Dept Genet & Bioinformat - Author

Orebro Univ, Sch Med Sci - Author

QIMR Berghofer Med Res Inst, Brisbane - Author

QIMR Berghofer Med Res Inst, Translat Neurogen Lab, Brisbane - Author

Queensland Ctr Mental Hlth Res, Wacol - Author

Queensland Univ Technol, Sch Psychol & Counselling, Brisbane - Author

Radboud Univ Nijmegen Med Ctr, Dept Human Genet - Author

Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav - Author

Royal Holloway Univ London, Dept Psychol - Author

Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Psychiat - Author

Spanish Consortium Res Epidemiol & Publ Hlth CIBE - Author

Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam UMC,Acad Med Ctr - Author

Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Publ & Occupat Hlth - Author

Univ Autonoma Barcelona, Dept Psychiat & Legal Med - Author

Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Grp Psychiat Mental Hlth & Addict, Psychiat Genet Unit - Author

Univ Barcelona UB, Fac Biol, Dept Genet Microbiol & Stat - Author

Univ Bergen, Dept Biomed, KG Jebsen Ctr Neuropsychiat Disorders - Author

Univ Bergen, Dept Clin Sci - Author

Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol - Author

Univ Bristol, MRC Integrat Epidemiol Unit, Bristol - Author

Univ Calif Los Angeles, Dept Comp Sci - Author

Univ Calif San Diego, Dept Psychiat - Author

Univ Colorado, Dept Ecol & Evolutionary Biol - Author

Univ Colorado, Dept Mol Cellular & Dev Biol - Author

Univ Colorado, Dept Psychol & Neurosci - Author

Univ Colorado, Inst Behav Genet - Author

Univ Colorado, Sch Med - Author

Univ Copenhagen, Dept Biol, Bioinformat Ctr - Author

Univ Copenhagen, Dept Clin Med - Author

Univ Florida, Dept Biostat - Author

Univ Gothenburg, Ctr Eth Law & Mental Hlth - Author

Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol - Author

Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Interdisciplinary Ctr Psychopathol & Emot Regulat - Author

Univ Helsinki, Fac Med, Dept Publ Hlth - Author

Univ Helsinki, HiLife, Inst Mol Med Finland FIMM - Author

Univ Kentucky, Ctr Innovat Publ Hlth - Author

Univ Melbourne, Allergy & Lung Hlth Unit, Melbourne Sch Populat & Global Hlth, Melbourne - Author

Univ Minnesota, Dept Psychol - Author

Univ Oslo, Inst Clin Med - Author

Univ Otago, Carney Ctr Pharmacogen - Author

Univ Otago, Christchurch Hlth & Dev Study, Dept Psychol Med - Author

Univ Otago, Dept Pathol & Biomed Sci, Biostat & Computat Biol Unit - Author

Univ Otago, Dunedin Multidisciplinary Hlth & Dev Res Unit - Author

Univ Oulu, Fac Med - Author

Univ Queensland, Inst Mol Biosci, Brisbane - Author

Univ Queensland, Queensland Brain Inst, Inst Mol Biosci, St Lucia - Author

Univ Queensland, Sch Psychol, Brisbane - Author

Univ Queensland, Sch Publ Hlth, Herston - Author

Univ Queensland, Social Sci Res Inst, Brisbane - Author

Univ Utah, Sch Med, Dept Psychiat - Author

Univ Utrecht, Dept Methodol & Stat - Author

Univ Valencia, Dept Nursing - Author

Univ Vermont, Dept Psychiat, Coll Med - Author

Univ Western Australia, Kids Res Inst Australia, Perth - Author

Virginia Commonwealth Univ, Coll Behav & Emot Hlth Inst - Author

Virginia Commonwealth Univ, Dept Human & Mol Genet - Author

Virginia Commonwealth Univ, Massey Canc Ctr - Author

Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat - Author

Vrije Univ Amsterdam, Amsterdam Neurosci, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet - Author

Vrije Univ Amsterdam, Dept Biol Psychol - Author

Abstract

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 (ADHD(SYMP)). Next, we meta-analyzed the results with a study of ADHD diagnosis (ADHD(OVERALL)). ADHD(SYMP) returned no genome-wide significant variants. We show that the combined ADHD(OVERALL) 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 (r(g) < -0.40) were observed with multiple cognitive traits. In three cohorts, polygenic scores (PGSs) based on ADHD(OVERALL) 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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Keywords

Attention-deficit/hyperactivity disorderDeficit hyperactivity disorderInformantPrediction

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal NATURE GENETICS due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 2/192, thus managing to position itself as a Q1 (Primer Cuartil), in the category Genetics & Heredity. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-04:

WoS: 6
Scopus: 3

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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Australia; Denmark; Finland; Germany; Netherlands; New Zealand; Norway; Singapore; Sweden; United Kingdom; United States of America.

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

Affiliations

Abstract

Keywords

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

Leadership analysis of institutional authors

Indexed in

APC

Citations

Altmetrics

Analysis of institutional authors

Share

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

Affiliations

Abstract

Keywords

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

Impact and social visibility

Leadership analysis of institutional authors