| Literature DB >> 30692689 |
Andrew J Schork1,2, Hyejung Won3,4,5,6,7, Vivek Appadurai1,2, Ron Nudel1,2, Mike Gandal3,4,5, Olivier Delaneau8,9,10, Malene Revsbech Christiansen11, David M Hougaard2,12, Marie Bækved-Hansen2,12, Jonas Bybjerg-Grauholm2,12, Marianne Giørtz Pedersen2,13,14, Esben Agerbo2,13,14, Carsten Bøcker Pedersen2,13,14, Benjamin M Neale15,16,17, Mark J Daly15,16,17, Naomi R Wray18,19, Merete Nordentoft2,20,21, Ole Mors2,22, Anders D Børglum2,23,24, Preben Bo Mortensen2,13,14,24, Alfonso Buil1,2, Wesley K Thompson1,2,25, Daniel H Geschwind3,4,5,26, Thomas Werge27,28,29.
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.Entities:
Mesh：
Year: 2019 PMID： 30692689 PMCID： PMC6497521 DOI： 10.1038/s41593-018-0320-0
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884