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Cross-Disorder Working Group, of the Psychiatric Genomics Consortium, Gordon-Smith, Katherine 
ORCID: https://orcid.org/0000-0003-4083-1143, Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334 and Perry, Amy ORCID: https://orcid.org/0000-0002-9381-6636
(2019)
Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders.
Cell, 179 (7).
1469-1482.e11.
ISSN 0092-8674 ESSN: 1097-4172
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AAM-with-cover-9156-Gordon-Smith-Jones-Perry-genomic-relationships-novel-loci-pleiotropic-mechanisms-across-eight-psychiatric-disorders.pdf - Accepted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (627kB) | Preview |
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: | Article |
|---|---|
| Additional Information: | Staff and students at the University of Worcester can access the full-text of the online published article via the official URL. External users should check availability with their local library or Interlibrary Requests Service. |
| Uncontrolled Discrete Keywords: | cross-disorder genetics, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, psychiatric genetics |
| Subjects: | B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
| Divisions: | College of Health, Life and Environmental Sciences > School of Allied Health and Community |
| Related URLs: | |
| Depositing User: | Katherine Gordon-Smith |
| Date Deposited: | 12 Feb 2020 12:18 |
| Last Modified: | 12 Dec 2020 01:00 |
| URI: | https://eprints.worc.ac.uk/id/eprint/9156 |
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