Integrative analyses highlight functional regulatory variants associated with neuropsychiatric diseases.

Humans Autism Spectrum Disorder / genetics Bipolar Disorder / genetics Schizophrenia / genetics Obsessive-Compulsive Disorder / genetics Depressive Disorder, Major / genetics Attention Deficit Disorder with Hyperactivity / genetics

Journal

Nature genetics

ISSN: 1546-1718

Titre abrégé: Nat Genet

Pays: United States

ID NLM: 9216904

Informations de publication

Date de publication:
Nov 2023

Historique:

received: 24 06 2021

accepted: 15 09 2023

medline: 10 11 2023

pubmed: 20 10 2023

entrez: 19 10 2023

Statut: ppublish

Résumé

Noncoding variants of presumed regulatory function contribute to the heritability of neuropsychiatric disease. A total of 2,221 noncoding variants connected to risk for ten neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, major depression, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder and schizophrenia, were studied in developing human neural cells. Integrating epigenomic and transcriptomic data with massively parallel reporter assays identified differentially-active single-nucleotide variants (daSNVs) in specific neural cell types. Expression-gene mapping, network analyses and chromatin looping nominated candidate disease-relevant target genes modulated by these daSNVs. Follow-up integration of daSNV gene editing with clinical cohort analyses suggested that magnesium transport dysfunction may increase neuropsychiatric disease risk and indicated that common genetic pathomechanisms may mediate specific symptoms that are shared across multiple neuropsychiatric diseases.

Identifiants

DOI: 10.1038/s41588-023-01533-5 PMID: 37857935

pubmed: 37857935

doi: 10.1038/s41588-023-01533-5

pii: 10.1038/s41588-023-01533-5

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1876-1891

Subventions

Organisme : NIA NIH HHS

ID : R01 AG066490

Pays : United States

Organisme : NIMH NIH HHS

ID : R01 MH125244

Pays : United States

Informations de copyright

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