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

Publication ,  Journal Article
van der Laan, CM; Ip, HF; Schipper, M; Hottenga, J-J; St Pourcain, B; Zayats, T; Pool, R; Krapohl, EML; Brikell, I; Soler Artigas, M; Llonga, N ...
Published in: Nat Genet
October 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.

Duke Scholars

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2025

Volume

57

Issue

10

Start / End Page

2427 / 2435

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Multifactorial Inheritance
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Developmental Biology
  • Child
  • Attention Deficit Disorder with Hyperactivity
 

Citation

APA
Chicago
ICMJE
MLA
NLM
van der Laan, C. M., Ip, H. F., Schipper, M., Hottenga, J.-J., St Pourcain, B., Zayats, T., … Boomsma, D. I. (2025). Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes. Nat Genet, 57(10), 2427–2435. https://doi.org/10.1038/s41588-025-02295-y
Laan, Camiel M. van der, Hill F. Ip, Marijn Schipper, Jouke-Jan Hottenga, Beate St Pourcain, Tetyana Zayats, René Pool, et al. “Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.Nat Genet 57, no. 10 (October 2025): 2427–35. https://doi.org/10.1038/s41588-025-02295-y.
van der Laan CM, Ip HF, Schipper M, Hottenga J-J, St Pourcain B, Zayats T, et al. Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes. Nat Genet. 2025 Oct;57(10):2427–35.
van der Laan, Camiel M., et al. “Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes.Nat Genet, vol. 57, no. 10, Oct. 2025, pp. 2427–35. Pubmed, doi:10.1038/s41588-025-02295-y.
van der Laan CM, Ip HF, Schipper M, Hottenga J-J, St Pourcain B, Zayats T, Pool R, Krapohl EML, Brikell I, Soler Artigas M, 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 X, 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 Ø, 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 M-J, Bønnelykke 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 M-R, 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, Davey Smith G, Hartman CA, Oldehinkel AJ, Casas M, Ribasés M, Lichtenstein P, Lundström S, Plomin R, Bartels M, Nivard MG, Boomsma DI. Genome-wide association meta-analysis of childhood ADHD symptoms and diagnosis identifies new loci and potential effector genes. Nat Genet. 2025 Oct;57(10):2427–2435.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2025

Volume

57

Issue

10

Start / End Page

2427 / 2435

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Multifactorial Inheritance
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
  • Developmental Biology
  • Child
  • Attention Deficit Disorder with Hyperactivity