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

The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium; International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)

doi:10.1038/nn.3922

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

The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium
, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)

Regeneron Pharmaceuticals, Inc.
Broad Institute
Massachusetts General Hospital
University of California at Los Angeles
King's College London
South London and Maudsley NHS Foundation Trust
Icahn School of Medicine at Mount Sinai
Vrije Universiteit Amsterdam
VU University Medical Center
Erasmus University Rotterdam
Indiana University Bloomington
University of Queensland
SUNY Upstate Medical University
Queensland Centre for Mental Health Research
Cardiff University
Biosciences Research Division
University of Melbourne
University of California at San Francisco
HudsonAlpha Institute for Biotechnology
University of Oslo
Diakonhjemmet Hospital
University of Michigan, Ann Arbor
Emory University
University College London
Trinity College Dublin
Johns Hopkins University
University of Coimbra
Karolinska Institutet
The University of Chicago
University of British Columbia
Heidelberg University
Cornell University
GlaxoSmithKline
Portland VA Medical Center
IRCCS Fondazione Stella Maris - Calambrone (Pisa)
Technische Universität Dresden
Parc Científic de Barcelona
Institut national de la santé et de la recherche médicale
Université Paris Cité
Assistance publique – Hôpitaux de Paris
Fondation FondaMental
University of Pennsylvania
CNRS
Sorbonne Université
Max Planck Institute of Psychiatry
University of Iowa
University of Edinburgh
Scripps Research Translational Institute
Scripps Health
University of Amsterdam
University of Groningen
Louisiana State University Health Sciences Center
Radboud University Nijmegen
University of California at Irvine
NCIRE (Northern California Institute of Q Research and Education)
University of Birmingham
Utrecht University
University Hospital Vall d'Hebron
Autonomous University of Barcelona
University of Bonn
Jülich Research Centre
University of Basel
iPSYCH
Aarhus University
Washington University St. Louis
University of Illinois at Chicago
University of Utah
University of Barcelona
Centro de Investigación en Red de Enfermedades Raras (CIBERER)
Translational Genomics Research Institute
University of Toronto
University of Miami
Queen Mary University of London
Munich Cluster for Systems Neurology (SyNergy)
Autism Speaks Inc.
University of North Carolina at Chapel Hill
University of Dundee
NorthShore University HealthSystem
London School of Hygiene and Tropical Medicine
Goethe University Frankfurt
National University of Singapore
University College Dublin
Georgetown University
Virginia Commonwealth University
Newcastle University
Oregon Health and Science University
University of Colorado Anschutz Medical Campus
Martin Luther University Halle-Wittenberg
Queensland Institute of Medical Research
University of Plymouth
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University of Minnesota Twin Cities
Vanderbilt University
Children's Hospital of Philadelphia
Stanford University
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University of Copenhagen
The University of Sydney
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German Cancer Research Center
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Geisinger Medical Center
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Feinstein Institute of Medical Research
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Columbia University
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Yale University
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Brown University
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Wellcome Trust Sanger Institute
Vall d'Hebron Research Institute
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Harvard University
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Instituto Gulbenkian de Medicina Molecular
Nationwide Children’s Hospital
Boston Children's Hospital
Leiden University
Department of Veterans Affairs

Research output: Contribution to journal › Article › peer-review

620 Citations (Scopus)

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.

Original language	English
Pages (from-to)	199-209
Number of pages	11
Journal	Nature Neuroscience
Volume	18
Issue number	2
DOIs	https://doi.org/10.1038/nn.3922
Publication status	Published - 19 Jan 2015
Externally published	Yes

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10.1038/nn.3922

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@article{634ac322707846e7900eb6a50f2f88c8,

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

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.",

author = "\{The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium\} and \{International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)\} and Colm O{\textquoteright}dushlaine and Lizzy Rossin and Lee, \{Phil H.\} and Laramie Duncan and Parikshak, \{Neelroop N.\} and Stephen Newhouse and Stephan Ripke and Neale, \{Benjamin M.\} and Purcell, \{Shaun M.\} and Danielle Posthuma and Nurnberger, \{John I.\} and Lee, \{S. Hong\} and Faraone, \{Stephen V.\} and Perlis, \{Roy H.\} and Mowry, \{Bryan J.\} and Anita Thapar and Goddard, \{Michael E.\} and Witte, \{John S.\} and Devin Absher and Ingrid Agartz and Huda Akil and Farooq Amin and Andreassen, \{Ole A.\} and Adebayo Anjorin and Richard Anney and Verneri Anttila and Arking, \{Dan E.\} and Philip Asherson and Azevedo, \{Maria H.\} and Lena Backlund and Badner, \{Judith A.\} and Bailey, \{Anthony J.\} and Tobias Banaschewski and Barchas, \{Jack D.\} and Barnes, \{Michael R.\} and Barrett, \{Thomas B.\} and Nicholas Bass and Agatino Battaglia and Michael Bauer and M{\`o}nica Bay{\'e}s and Frank Bellivier and Bergen, \{Sarah E.\} and Wade Berrettini and Catalina Betancur and Thomas Bettecken and Joseph Biederman and Binder, \{Elisabeth B.\} and Black, \{Donald W.\} and Blackwood, \{Douglas H.R.\} and Hottenga, \{Jouke Jan\}",

year = "2015",

month = jan,

day = "19",

doi = "10.1038/nn.3922",

language = "English",

volume = "18",

pages = "199--209",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Research",

number = "2",

}

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. / The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium; International Inflammatory Bowel Disease Genetics Consortium (IIBDGC).
In: Nature Neuroscience, Vol. 18, No. 2, 19.01.2015, p. 199-209.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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AU - The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium

AU - International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)

AU - O’dushlaine, Colm

AU - Rossin, Lizzy

AU - Lee, Phil H.

AU - Duncan, Laramie

AU - Parikshak, Neelroop N.

AU - Newhouse, Stephen

AU - Ripke, Stephan

AU - Neale, Benjamin M.

AU - Purcell, Shaun M.

AU - Posthuma, Danielle

AU - Nurnberger, John I.

AU - Lee, S. Hong

AU - Faraone, Stephen V.

AU - Perlis, Roy H.

AU - Mowry, Bryan J.

AU - Thapar, Anita

AU - Goddard, Michael E.

AU - Witte, John S.

AU - Absher, Devin

AU - Agartz, Ingrid

AU - Akil, Huda

AU - Amin, Farooq

AU - Andreassen, Ole A.

AU - Anjorin, Adebayo

AU - Anney, Richard

AU - Anttila, Verneri

AU - Arking, Dan E.

AU - Asherson, Philip

AU - Azevedo, Maria H.

AU - Backlund, Lena

AU - Badner, Judith A.

AU - Bailey, Anthony J.

AU - Banaschewski, Tobias

AU - Barchas, Jack D.

AU - Barnes, Michael R.

AU - Barrett, Thomas B.

AU - Bass, Nicholas

AU - Battaglia, Agatino

AU - Bauer, Michael

AU - Bayés, Mònica

AU - Bellivier, Frank

AU - Bergen, Sarah E.

AU - Berrettini, Wade

AU - Betancur, Catalina

AU - Bettecken, Thomas

AU - Biederman, Joseph

AU - Binder, Elisabeth B.

AU - Black, Donald W.

AU - Blackwood, Douglas H.R.

AU - Hottenga, Jouke Jan

PY - 2015/1/19

Y1 - 2015/1/19

N2 - 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.

AB - 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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DO - 10.1038/nn.3922

M3 - Article

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AN - SCOPUS:84923077204

SN - 1097-6256

VL - 18

SP - 199

EP - 209

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 2

ER -

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

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