Population-based Risk of Psychiatric Disorders Associated with Recurrent CNVs.


Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
05 Sep 2023
Historique:
pubmed: 27 10 2023
medline: 27 10 2023
entrez: 27 10 2023
Statut: epublish

Résumé

Recurrent copy number variants (rCNVs) are associated with increased risk of neuropsychiatric disorders but their pathogenic population-level impact is unknown. We provide population-based estimates of rCNV-associated risk of neuropsychiatric disorders for 34 rCNVs in the iPSYCH2015 case-cohort sample (n=120,247). Most observed significant increases in rCNV-associated risk for ADHD, autism or schizophrenia were moderate (HR:1.42-5.00), and risk estimates were highly correlated across these disorders, the most notable exception being high autism-associated risk with Prader-Willi/Angelman Syndrome duplications (HR=20.8). No rCNV was associated with significant increase in depression risk. Also, rCNV-associated risk was positively correlated with locus size and gene constraint. Comparison with published rCNV studies suggests that prevalence of some rCNVs is higher, and risk of psychiatric disorders lower, than previously estimated. In an era where genetics is increasingly being clinically applied, our results highlight the importance of population-based risk estimates for genetics-based predictions.

Identifiants

pubmed: 37886536
doi: 10.1101/2023.09.04.23294975
pmc: PMC10602037
pii:
doi:

Types de publication

Preprint

Langues

eng

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Auteurs

Morteza Vaez (M)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

Simone Montalbano (S)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

Xabier Calle Sánchez (XC)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

Kajsa-Lotta Georgii Hellberg (KL)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

Saeid Rasekhi Dehkordi (S)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

Morten Dybdahl Krebs (M)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

Joeri Meijsen (J)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

John Shorter (J)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
Department of Science and Environment, Roskilde University, DK-4000 Roskilde, Denmark.

Jonas Byberg-Grauholm (J)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, DK-2300 Copenhagen, Denmark.

Preben B Mortensen (PB)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
National Centre for Register-based Research, Aarhus University, DK-8210 Aarhus, Denmark.

Anders D Børglum (AD)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Department of Biomedicine-Human Genetics and the iSEQ Center, Aarhus University, DK-8000 Aarhus, Denmark.
Center for Genomics and Personalized Medicine, DK-8000 Aarhus, Denmark.

David M Hougaard (DM)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, DK-2300 Copenhagen, Denmark.

Merete Nordentoft (M)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Mental Health Center Copenhagen, Copenhagen University Hospital, DK-2400 Copenhagen, Denmark.

Daniel H Geschwind (DH)

Department of Neurology, University of California, Los Angeles, CA, USA.
Department of Human Genetics, University of California, Los Angeles, CA, USA.
Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA.
Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, USA.
Center for Human Development, University of California, San Diego, CA, USA.

Alfonso Buil (A)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Lundbeck Foundation Center for GeoGenetics, GLOBE Institute, University of Copenhagen, DK-1350 Copenhagen, Denmark.

Andrew J Schork (AJ)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Lundbeck Foundation Center for GeoGenetics, GLOBE Institute, University of Copenhagen, DK-1350 Copenhagen, Denmark.
Neurogenomics Division, The Translational Genomics Research Institute (TGEN), Phoenix, AZ, USA.

Dorte Helenius (D)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.

Armin Raznahan (A)

Section on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.

Wesley K Thompson (WK)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Laureate Institute for Brain Research, Tulsa, OK, USA.

Thomas Werge (T)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Lundbeck Foundation Center for GeoGenetics, GLOBE Institute, University of Copenhagen, DK-1350 Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Andrés Ingason (A)

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, DK-4000 Roskilde, Denmark.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen and Aarhus, Denmark.
Lundbeck Foundation Center for GeoGenetics, GLOBE Institute, University of Copenhagen, DK-1350 Copenhagen, Denmark.

Classifications MeSH