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Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways


Network and Pathway Analysis Subgroup of Psychiatric Genomics Co; et al; Steinhausen, Hans-Christoph (2015). Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nature Neuroscience, 18(2):199-209.

Abstract

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Abstract

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

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80 citations in Web of Science®
108 citations in Scopus®
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Additional indexing

Contributors:The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:February 2015
Deposited On:11 Dec 2015 16:03
Last Modified:05 Apr 2016 19:37
Publisher:Nature Publishing Group
ISSN:1097-6256
Publisher DOI:https://doi.org/10.1038/nn.3922
PubMed ID:25599223

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