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

, Cross-Disorder Group of the Psychiatric Genomics Consortium. Ele (2019) Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell, 179 (7). 1469-1482.e11. ISSN 0092-8674

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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.

Item Type:
Journal Article
Journal or Publication Title:
Cell
Additional Information:
This is the author’s version of a work that was accepted for publication in Cell. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cell, 179, 7, 2019 DOI: 10.1016/j.cell.2019.11.020
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300
Subjects:
ID Code:
139967
Deposited By:
Deposited On:
07 Jan 2020 15:05
Refereed?:
Yes
Published?:
Published
Last Modified:
27 Oct 2020 09:38