Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.

Humans Genome-Wide Association Study Attention Deficit Disorder with Hyperactivity / genetics Brain Cognition Genetic Predisposition to Disease

Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
02 2023
Historique:
received: 28 01 2022
accepted: 09 12 2022
pubmed: 27 1 2023
medline: 16 2 2023
entrez: 26 1 2023
Statut: ppublish

Résumé

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

Identifiants

DOI: 10.1038/s41588-022-01285-8 PMID: 36702997
pubmed: 36702997
doi: 10.1038/s41588-022-01285-8
pii: 10.1038/s41588-022-01285-8
doi:

Types de publication

Meta-Analysis Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

198-208

Subventions

Organisme : NIMH NIH HHS
ID : R37 MH107649
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH087004
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109514
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH116442
Pays : United States

Investigateurs

Alexandra Havdahl (A)
Alysa Doyle (A)
Andreas Reif (A)
Anita Thapar (A)
Bru Cormand (B)
Calwing Liao (C)
Christie Burton (C)
Claiton H D Bau (CHD)
Diego Luiz Rovaris (DL)
Edmund Sonuga-Barke (E)
Elizabeth Corfield (E)
Eugenio Horacio Grevet (EH)
Henrik Larsson (H)
Ian R Gizer (IR)
Irwin Waldman (I)
Isabell Brikell (I)
Jan Haavik (J)
Jennifer Crosbie (J)
James McGough (J)
Jonna Kuntsi (J)
Joseph Glessner (J)
Kate Langley (K)
Klaus-Peter Lesch (KP)
Luis Augusto Rohde (LA)
Mara H Hutz (MH)
Marieke Klein (M)
Mark Bellgrove (M)
Martin Tesli (M)
Michael C O'Donovan (MC)
Ole Andreas Andreassen (OA)
Patrick W L Leung (PWL)
Pedro M Pan (PM)
Ridha Joober (R)
Russel Schachar (R)
Sandra Loo (S)
Stephanie H Witt (SH)
Ted Reichborn-Kjennerud (T)
Tobias Banaschewski (T)
Ziarih Hawi (Z)
Mark J Daly (MJ)
Ole Mors (O)

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Ditte Demontis (D)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. ditte@biomed.au.dk.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. ditte@biomed.au.dk.
Center for Genomics and Personalized Medicine, Aarhus, Denmark. ditte@biomed.au.dk.
ORCID: 0000-0001-9124-2766

G Bragi Walters (GB)

deCODE Genetics/Amgen, Reykjavik, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
ORCID: 0000-0002-5415-6487

Georgios Athanasiadis (G)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Mental Health Centre Sct. Hans, Capital Region of Denmark, Institute of Biological Psychiatry, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Evolutionary Biology, Ecology and Environmental Sciences, University of Barcelona, Barcelona, Spain.
ORCID: 0000-0002-2927-4035

Raymond Walters (R)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0001-8422-6530

Karen Therrien (K)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0003-3351-7260

Trine Tollerup Nielsen (TT)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.

Leila Farajzadeh (L)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.

Georgios Voloudakis (G)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-5729-632X

Jaroslav Bendl (J)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0001-9989-2720

Biau Zeng (B)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Wen Zhang (W)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Jakob Grove (J)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
ORCID: 0000-0003-2284-5744

Thomas D Als (TD)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.
ORCID: 0000-0002-2963-1928

Jinjie Duan (J)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.

F Kyle Satterstrom (FK)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0001-6187-7680

Jonas Bybjerg-Grauholm (J)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
ORCID: 0000-0003-1705-4008

Marie Bækved-Hansen (M)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.

Olafur O Gudmundsson (OO)

deCODE Genetics/Amgen, Reykjavik, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
ORCID: 0000-0001-8466-1559

Sigurdur H Magnusson (SH)

deCODE Genetics/Amgen, Reykjavik, Iceland.
ORCID: 0000-0001-6669-3071

Gisli Baldursson (G)

Department of Child and Adolescent Psychiatry, National University Hospital, Reykjavik, Iceland.

Katrin Davidsdottir (K)

The Centre for Child Development and Behaviour, Capital Area Primary Health Care, Reykjavik, Iceland.

Gyda S Haraldsdottir (GS)

The Centre for Child Development and Behaviour, Capital Area Primary Health Care, Reykjavik, Iceland.

Esben Agerbo (E)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
National Centre for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark.
Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.
ORCID: 0000-0002-2849-524X

Gabriel E Hoffman (GE)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
ORCID: 0000-0002-0957-0224

Søren Dalsgaard (S)

National Centre for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark.
Mental Health Services of the Capital Region, Child and Adolescent Psychiatric Center, Glostrup, Denmark.
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
ORCID: 0000-0003-4659-0969

Joanna Martin (J)

Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
ORCID: 0000-0002-8911-3479

Marta Ribasés (M)

Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
ORCID: 0000-0003-1039-1116

Dorret I Boomsma (DI)

Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
ORCID: 0000-0002-7099-7972

Maria Soler Artigas (M)

Psychiatric Genetics Unit, Group of Psychiatry, Mental Health and Addiction, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
Department of Genetics, Microbiology, and Statistics, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
ORCID: 0000-0002-3213-1107

Nina Roth Mota (N)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
ORCID: 0000-0003-3504-759X

Daniel Howrigan (D)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-7721-4838

Sarah E Medland (SE)

Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
ORCID: 0000-0003-1382-380X

Tetyana Zayats (T)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
PROMENTA, Department of Psychology, University of Oslo, Oslo, Norway.

Veera M Rajagopal (VM)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.
ORCID: 0000-0002-5236-168X

Merete Nordentoft (M)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Mental Health Centre Copenhagen, Capital Region of Denmark, Copenhagen University Hospital, Copenhagen, Denmark.

Ole Mors (O)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Aarhus, Denmark.

David M Hougaard (DM)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
ORCID: 0000-0001-5928-3517

Preben Bo Mortensen (PB)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
National Centre for Register-Based Research, Business and Social Sciences, Aarhus University, Aarhus, Denmark.
Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.

Mark J Daly (MJ)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
ORCID: 0000-0002-0949-8752

Stephen V Faraone (SV)

Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.

Hreinn Stefansson (H)

deCODE Genetics/Amgen, Reykjavik, Iceland.

Panos Roussos (P)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mental Illness Research Education and Clinical Center, JJ Peters VA Medical Center, Bronx, NY, USA.
ORCID: 0000-0002-4640-6239

Barbara Franke (B)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.
Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.
ORCID: 0000-0003-4375-6572

Thomas Werge (T)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Mental Health Centre Sct. Hans, Capital Region of Denmark, Institute of Biological Psychiatry, Copenhagen University Hospital, Copenhagen, Denmark.
ORCID: 0000-0003-1829-0766

Benjamin M Neale (BM)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0003-1513-6077

Kari Stefansson (K)

deCODE Genetics/Amgen, Reykjavik, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
ORCID: 0000-0003-1676-864X

Anders D Børglum (AD)

Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. anders@biomed.au.dk.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. anders@biomed.au.dk.
Center for Genomics and Personalized Medicine, Aarhus, Denmark. anders@biomed.au.dk.
ORCID: 0000-0001-8627-7219

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genome-wide analyses of ADHD identify 27 risk...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide analyses of ADHD identify 27 risk...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles déficitaires de l'attention et du comportement perturbateur › Trouble déficitaire de l'attention avec hyperactivité › Genome-wide analyses of ADHD identify 27 risk...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Genome-wide analyses of ADHD identify 27 risk...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › Genome-wide analyses of ADHD identify 27 risk...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genome-wide analyses of ADHD identify 27 risk...