Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways.
Journal Article
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.
Full Text
Duke Authors
Published Date
- February 2015
Published In
Volume / Issue
- 18 / 2
Start / End Page
- 199 - 209
PubMed ID
- 25599223
Pubmed Central ID
- 25599223
Electronic International Standard Serial Number (EISSN)
- 1546-1726
Digital Object Identifier (DOI)
- 10.1038/nn.3922
Language
- eng
Conference Location
- United States