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

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Psychiat Genomics Consortium , 23andMe Res Team , Psychosis Endopheno-types Int Cons , Wellcome Trust Case Control Consor , Lee , P H , Anttila , V , Won , H , Kaprio , J , Keski-Rahkonen , A , Churchhouse , C , Rehnström , K , Raevuori , A , Palotie , A , Daly , M J & Neale , B M 2019 , ' Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders ' , Cell , vol. 179 , no. 7 , pp. 1469-1482.e11 . https://doi.org/10.1016/j.cell.2019.11.020

Title: Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
Author: Psychiat Genomics Consortium; 23andMe Res Team; Psychosis Endopheno-types Int Cons; Wellcome Trust Case Control Consor; Lee, Phil H.; Anttila, Verneri; Won, Hyejung; Kaprio, Jaakko; Keski-Rahkonen, Anna; Churchhouse, Claire; Rehnström, Karola; Raevuori, Anu; Palotie, Aarno; Daly, Mark J.; Neale, Benjamin M.
Contributor: University of Helsinki, Aarno Palotie / Principal Investigator
University of Helsinki, Jaakko Kaprio / Principal Investigator
University of Helsinki, University Management
University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2019-12-12
Language: eng
Number of pages: 25
Belongs to series: Cell
ISSN: 0092-8674
URI: http://hdl.handle.net/10138/328511
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/hyper-activity 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.
Subject: WIDE ASSOCIATION
HUMAN BRAIN
GENETIC CORRELATIONS
GENOTYPE IMPUTATION
INSIGHTS
IDENTIFICATION
TRANSCRIPTOME
DEMETHYLASE
MUTATIONS
DISEASES
1182 Biochemistry, cell and molecular biology
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