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

Journal article
Authors C O'Dushlaine
L Rossin
PH Lee
L Duncan
NN Parikshak
S Newhouse
S Ripke
BM Neale
SM Purcell
D Posthuma
Mikael Landén
Published in Nature neuroscience
Volume 18
Issue 2
Pages 199-209
ISSN 1546-1726
Publication year 2015
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 199-209
Language en
Links dx.doi.org/10.1038/nn.3922
Keywords Brain, immunology, metabolism, Databases, Genetic, Genetic Predisposition to Disease, genetics, Genome-Wide Association Study, methods, Histones, genetics, metabolism, Humans, Mental Disorders, etiology, genetics, Signal Transduction, genetics
Subject categories Psychiatry

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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