Author:
Schork Andrew J.,Won Hyejung,Appadurai Vivek,Nudel Ron,Gandal Mike,Delaneau Olivier,Hougaard David M.,Bækved-Hansen Marie,Bybjerg-Grauholm Jonas,Giørtz Pedersen Marianne,Agerbo Esben,Bøcker Pedersen Carsten,Neale Benjamin M.,Daly Mark J.,Nordentoft Merete,Mors Ole,Børglum Anders D.,Mortensen Preben Bo,Buil Alfonso,Thompson Wesley K.,Geschwind Daniel,Werge Thomas
Abstract
AbstractThere 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 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 SNP-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 midgestation. This epoch is supported by partitioning cross-disorder SNP-heritability which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings indicate that dysregulation of genes that direct neurodevelopment by common genetic variants results in general liability for many later psychiatric outcomes.
Publisher
Cold Spring Harbor Laboratory