Journal article

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

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 Show all

Nature Neuroscience | NATURE PUBLISHING GROUP | Published : 2015

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 sta..

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University of Melbourne Researchers

Grants

Awarded by US National Institute of Mental Health (NIMH)


Awarded by NIMH


Awarded by Netherlands Scientific Organization (NOW)


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by NATIONAL INSTITUTE OF MENTAL HEALTH


Awarded by Lundbeck Foundation


Awarded by Medical Research Council


Funding Acknowledgements

G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. The PGC Cross-Disorder Group is supported by NIMH grant U01 MH085520. Statistical analyses were carried out on the Genetic Cluster Computer, which is fmancially supported by the Netherlands Scientific Organization (NOW; 480-05-003; principal investigator D.P.) along with a supplement from the Dutch Brain Foundation and VU University. Numerous (> 100) grants from government agencies along with substantial private and foundation support worldwide enabled the collection of phenotype and genotype data, without which this research would not be possible.