Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups.

Attention Deficit Disorder with Hyperactivity / genetics Autism Spectrum Disorder / genetics Brain Genetic Predisposition to Disease Humans Phenotype

Journal

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

Informations de publication

Date de publication:
10 2022
Historique:
received: 01 06 2021
accepted: 20 06 2022
pubmed: 27 9 2022
medline: 12 10 2022
entrez: 26 9 2022
Statut: ppublish

Résumé

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.

Identifiants

DOI: 10.1038/s41588-022-01171-3 PMID: 36163277
pubmed: 36163277
doi: 10.1038/s41588-022-01171-3
pii: 10.1038/s41588-022-01171-3
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1470-1478

Subventions

Organisme : NIMH NIH HHS
ID : U01 MH109514
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH125050
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH116442
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH105500
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116037
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109677
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110427
Pays : United States
Organisme : NIAMS NIH HHS
ID : U01 AR076092
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH125246
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Manuel Mattheisen (M)

Department of Biomedicine - Human Genetics and the iSEQ Center, Aarhus University, Aarhus, Denmark. manuel.mattheisen@gmail.com.
Department of Community Health and Epidemiology & Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. manuel.mattheisen@gmail.com.
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany. manuel.mattheisen@gmail.com.
ORCID: 0000-0002-8442-493X

Jakob Grove (J)

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

Thomas D Als (TD)

Department of Biomedicine - Human Genetics and the iSEQ Center, 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

Joanna Martin (J)

MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

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, Department of Genetics and Genomic Sciences, 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.
ORCID: 0000-0002-5729-632X

Sandra Meier (S)

Department of Biomedicine - Human Genetics and the iSEQ Center, Aarhus University, Aarhus, Denmark.
Department of Community Health and Epidemiology & Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.

Ditte Demontis (D)

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

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, Department of Genetics and Genomic Sciences, 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.
ORCID: 0000-0001-9989-2720

Raymond Walters (R)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, 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

Caitlin E Carey (CE)

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

Anders Rosengren (A)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Institute of Biological Psychiatry, Mental Health Services Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
ORCID: 0000-0002-6682-1288

Nora I Strom (NI)

Department of Biomedicine - Human Genetics and the iSEQ Center, Aarhus University, Aarhus, Denmark.
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0002-5261-8852

Mads Engel Hauberg (ME)

Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn Institute for Data Science and Genomic Technology, Department of Genetics and Genomic Sciences, 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.
ORCID: 0000-0003-4873-2764

Biao 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, Department of Genetics and Genomic Sciences, 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.

Gabriel Hoffman (G)

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

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, Department of Genetics and Genomic Sciences, 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.

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 Bækvad-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.

Esben Agerbo (E)

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

Bru Cormand (B)

Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain.
Institut de Recerca Sant Joan de Déu (IR-SJD), Esplugues de Llobregat, Catalonia, Spain.
ORCID: 0000-0001-5318-4382

Merete Nordentoft (M)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
Copenhagen Research Centre for Mental Health (CORE), Mental Health Centre Copenhagen, Copenhagen, Denmark.
University Hospital, Hellerup, Denmark.

Thomas Werge (T)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Institute of Biological Psychiatry, Mental Health Services Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
GLOBE Institute, Center for GeoGenetics, University of Copenhagen, Copenhagen, Denmark.
ORCID: 0000-0003-1829-0766

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

Joseph D Buxbaum (JD)

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mindich Child Health and Development Institute, 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.
ORCID: 0000-0001-8898-8313

Stephen V Faraone (SV)

Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, NY, USA.
Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY, USA.

Barbara Franke (B)

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

Søren Dalsgaard (S)

National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
ORCID: 0000-0003-4659-0969

Preben B Mortensen (PB)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Center for Genomics and Personalized Medicine, Aarhus, Denmark.
National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.

Elise B Robinson (EB)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

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, Department of Genetics and Genomic Sciences, 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.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, JJ Peters VA Medical Center, Bronx, NY, USA.
ORCID: 0000-0002-4640-6239

Benjamin M Neale (BM)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, 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

Mark J Daly (MJ)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, 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.

Anders D Børglum (AD)

Department of Biomedicine - Human Genetics and the iSEQ Center, 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 › Troubles mentaux › Troubles du développement neurologique › Troubles déficitaires de l'attention et du comportement perturbateur › Trouble déficitaire de l'attention avec hyperactivité › Identification of shared and differentiating...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles généralisés du développement de l'enfant › Trouble du spectre autistique › Identification of shared and differentiating...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Identification of shared and differentiating...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Identification of shared and differentiating...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification of shared and differentiating...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Identification of shared and differentiating...