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)

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

602 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	199-209
Número de páginas	11
Publicación	Nature Neuroscience
Volumen	18
N.º	2
DOI	https://doi.org/10.1038/nn.3922
Estado	Published - feb. 17 2015
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
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 financially 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.

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

ASJC Scopus Subject Areas

General Neuroscience

Acceder al documento

10.1038/nn.3922

Otros archivos y enlaces

Citar esto

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).
En: Nature Neuroscience, Vol. 18, N.º 2, 17.02.2015, p. 199-209.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

@article{97d2a8599af74de5bf84fc109aeb83a2,

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 Sandra Meier",

note = "Funding Information: 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{\textquoteright}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 financially 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. Publisher Copyright: {\textcopyright} 2015 Nature America, Inc. All rights reserved.",

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",

number = "2",

}

TY - JOUR

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 - Meier, Sandra

N1 - Funding Information: 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 financially 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. Publisher Copyright: © 2015 Nature America, Inc. All rights reserved.

PY - 2015/2/17

Y1 - 2015/2/17

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.

UR - http://www.scopus.com/inward/record.url?scp=84923077204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923077204&partnerID=8YFLogxK

U2 - 10.1038/nn.3922

DO - 10.1038/nn.3922

M3 - Article

C2 - 25599223

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

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto