A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment.

Details

Serval ID
serval:BIB_976997F960DE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment.
Journal
Nature neuroscience
Author(s)
Schork A.J., Won H., Appadurai V., Nudel R., Gandal M., Delaneau O., Revsbech Christiansen M., Hougaard D.M., Bækved-Hansen M., Bybjerg-Grauholm J., Giørtz Pedersen M., Agerbo E., Bøcker Pedersen C., Neale B.M., Daly M.J., Wray N.R., Nordentoft M., Mors O., Børglum A.D., Bo Mortensen P., Buil A., Thompson W.K., Geschwind D.H., Werge T.
ISSN
1546-1726 (Electronic)
ISSN-L
1097-6256
Publication state
Published
Issued date
03/2019
Peer-reviewed
Oui
Volume
22
Number
3
Pages
353-361
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Brain/embryology, Brain/metabolism, Cohort Studies, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mental Disorders/genetics, Polymorphism, Single Nucleotide, Risk Factors
Pubmed
Web of science
Create date
16/01/2020 12:49
Last modification date
17/01/2020 7:26
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