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

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Author(s)

Colm O'Dushlaine, Lizzy Rossin, Phil H. Lee, Laramie Duncan, Neelroop N. Parikshak, Stephen Newhouse, Stephan Ripke, Benjamin M. Neale, Shaun M. Purcell, Danielle Posthuma, John I. Nurnberger, S. Hong Lee, Stephen V. Faraone, Roy H. Perlis, Bryan J. Mowry, Anita Thapar, Michael E. Goddard, John S. Witte, Devin Absher, Ingrid Agartz & 32 others Huda Akil, Farooq Amin, Ole A. Andreassen, Adebayo Anjorin, Richard Anney, Verneri Anttila, Dan E. Arking, Philip Asherson, Maria H. Azevedo, Lena Backlund, Judith A. Badner, Anthony J. Bailey, Tobias Banaschewski, Jack D. Barchas, Michael R. Barnes, Thomas B. Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Monica Bayes, Frank Bellivier, Sarah E. Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B. Binder, Donald W. Black, Douglas H. R. Blackwood, Lindsey Kent, IIBDGC, Network & Pathway Anal Subgrp Psyc

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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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Details

Original languageEnglish
Pages (from-to)199-209
Number of pages11
JournalNature Neuroscience
Volume18
Issue number2
Early online date19 Jan 2015
DOIs
Publication statusPublished - Feb 2015

    Research areas

  • De-novo mutations, Schizophrenia, Methylation, Disorders, Autism, Brain, Promoters, Burden, Loci

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