Authors
Bernie Devlin, John R Kelsoe, Pamela Sklar, Mark J Daly, Michael C O'Donovan, Nicholas Craddock, Kenneth S Kendler, Lauren A Weiss, Naomi R Wray, Zhongming Zhao, Daniel H Geschwind, Patrick F Sullivan, Jordan W Smoller, Peter A Holmans, Gerome Breen
Publication date
2015/2
Journal
Nature neuroscience
Volume
18
Issue
2
Pages
199-209
Publisher
Nature Publishing Group US
Description
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 …
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