Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
received:
10
07
2021
accepted:
25
10
2023
medline:
1
12
2023
pubmed:
1
12
2023
entrez:
30
11
2023
Statut:
aheadofprint
Résumé
Attention deficit hyperactivity disorder (ADHD) is a complex disorder that manifests variability in long-term outcomes and clinical presentations. The genetic contributions to such heterogeneity are not well understood. Here we show several genetic links to clinical heterogeneity in ADHD in a case-only study of 14,084 diagnosed individuals. First, we identify one genome-wide significant locus by comparing cases with ADHD and autism spectrum disorder (ASD) to cases with ADHD but not ASD. Second, we show that cases with ASD and ADHD, substance use disorder and ADHD, or first diagnosed with ADHD in adulthood have unique polygenic score (PGS) profiles that distinguish them from complementary case subgroups and controls. Finally, a PGS for an ASD diagnosis in ADHD cases predicted cognitive performance in an independent developmental cohort. Our approach uncovered evidence of genetic heterogeneity in ADHD, helping us to understand its etiology and providing a model for studies of other disorders.
Identifiants
pubmed: 38036780
doi: 10.1038/s41588-023-01593-7
pii: 10.1038/s41588-023-01593-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R335-2019-2318
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R208-2015-3951
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R102-A9118
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R155-2014-1724
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U24AG051129S1
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : UH2AG064706
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : UH2AG064706S1
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041022
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041028
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041048
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041089
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041106
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041117
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041120
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041134
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041148
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041156
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01DA041174
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U24DA041123
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U24DA041147
Organisme : Fonden for Faglig Udvikling af Speciallægepraksis
ID : 38850/16
Organisme : Simons Foundation
ID : SFARI 311789
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : 5U01MH094432-02
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 667302
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 847879
Organisme : Helsefonden (Health Foundation)
ID : 19-8-0260
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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