A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
13
01
2018
accepted:
06
12
2018
pubmed:
30
1
2019
medline:
22
5
2019
entrez:
30
1
2019
Statut:
ppublish
Résumé
There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here we leverage the unique Integrative Psychiatric Research Consortium (iPSYCH) study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder single-nucleotide polymorphism heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during mid-gestation. This epoch is supported by partitioning cross-disorder single-nucleotide polymorphism heritability, which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings suggest that dysregulation of genes that direct neurodevelopment by common genetic variants may result in general liability for many later psychiatric outcomes.
Identifiants
pubmed: 30692689
doi: 10.1038/s41593-018-0320-0
pii: 10.1038/s41593-018-0320-0
pmc: PMC6497521
mid: NIHMS1015642
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-361Subventions
Organisme : NIMH NIH HHS
ID : R01 MH094714
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM104400
Pays : United States
Organisme : NIMH NIH HHS
ID : R00 MH113823
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110927
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH094432
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109912
Pays : United States
Commentaires et corrections
Type : CommentIn
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