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Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Authors
 Cross-Disorder Group of the Psychiatric Genomics Consortium 
Citation
 CELL, Vol.179(7) : 1469-1482.e11, 2019 
Journal Title
 CELL 
ISSN
 0092-8674 
Issue Date
2019
Keywords
GWAS ; Psychiatric genetics ; cross-disorder genetics ; functional genomics ; gene expression ; genetic architecture ; genetic correlation ; neurodevelopment ; pleiotropy ; psychiatric disorders
Abstract
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
Full Text
https://www.sciencedirect.com/science/article/pii/S0092867419312760
DOI
10.1016/j.cell.2019.11.020
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
Yonsei Authors
Song, Dong Ho(송동호) ORCID logo https://orcid.org/0000-0002-9647-3130
Cheon, Keun Ah(천근아) ORCID logo https://orcid.org/0000-0001-7113-9286
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174669
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