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)

Department of Statistics

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

589 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 - 2015 Feb 17

All Science Journal Classification (ASJC) codes

General Neuroscience

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10.1038/nn.3922

Cite this

@article{937850dd48d94f92bca54015e9ded9aa,

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 Tzeng, {Jung Ying}",

year = "2015",

month = feb,

day = "17",

doi = "10.1038/nn.3922",

language = "English",

volume = "18",

pages = "199--209",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

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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, 17.02.2015, p. 199-209.

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

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T1 - Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

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 - Tzeng, Jung Ying

PY - 2015/2/17

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

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