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

Publication ,  Journal Article
Published in: Nat Neurosci
February 2015

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.

Duke Scholars

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Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

February 2015

Volume

18

Issue

2

Start / End Page

199 / 209

Location

United States

Related Subject Headings

  • Signal Transduction
  • Neurology & Neurosurgery
  • Mental Disorders
  • Humans
  • Histones
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Databases, Genetic
  • Brain
  • 5202 Biological psychology
 

Citation

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Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. (2015). Nat Neurosci, 18(2), 199–209. https://doi.org/10.1038/nn.3922
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways.Nat Neurosci 18, no. 2 (February 2015): 199–209. https://doi.org/10.1038/nn.3922.
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways.Nat Neurosci, vol. 18, no. 2, Feb. 2015, pp. 199–209. Pubmed, doi:10.1038/nn.3922.

Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

February 2015

Volume

18

Issue

2

Start / End Page

199 / 209

Location

United States

Related Subject Headings

  • Signal Transduction
  • Neurology & Neurosurgery
  • Mental Disorders
  • Humans
  • Histones
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Databases, Genetic
  • Brain
  • 5202 Biological psychology