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

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiolo...

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Published inNature neuroscience Vol. 18; no. 2; pp. 199 - 209
Main Authors O'Dushlaine, C., Rossin, L., Lee P., H., Duncan, L., Parikshak N., N., Newhouse, S., Ripke, S., Neale B., M., Purcell S., M., Posthuma, D., Nurnberger J., I., Lee S., H., Faraone S., V., Perlis R., H., Mowry B., J., Thapar, A., Goddard M., E., Witte J., S., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen O., A., Anjorin, A., Anney, R., Anttila, V., Arking D., E., Asherson, P., Azevedo M., H., Backlund, L., Badner J., A., Bailey A., J., Banaschewski, T., Barchas J., D., Barnes M., R., Barrett T., B., Bass, N., Battaglia, A., Bauer, M., Bayés, M., Bellivier, F., Bergen S., E., Berrettini, W., Betancur, Catalina, Bettecken, T., Biederman, J., Binder E., B., Black D., W., Blackwood D., H., Bloss C., S., Boehnke, M., Boomsma D., I., Breuer, R., Bruggeman, R., Cormican, P., Buccola N., G., Buitelaar J., K., Bunney W., E., Buxbaum J., D., Byerley W., F., Byrne E., M., Caesar, S., Cahn, W., Cantor R., M., Casas, M., Chakravarti, A., Chambert, K., Choudhury, K., Cichon, S., Mattheisen, M., Cloninger C., R., Collier D., A., Cook E., H., Coon, H., Cormand, B., Corvin, A., Coryell W., H., Craig D., W., Craig I., W., Crosbie, J., Cuccaro M., L., Curtis, D., Czamara, D., Datta, S., Dawson, G., Day, R., de Geus E., J., Degenhardt, F., Djurovic, S., Donohoe G., J., Doyle A., E., Duan, J., Dudbridge, F., Duketis, E., Ebstein R., P., Edenberg H., J., Elia, J., Ennis, S., Etain, B., Fanous, F.
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.02.2015
Nature Publishing Group
Subjects
631/114/2415
631/208/205/2138
631/378/1689/1414
631/378/1689/1799
Animal Genetics and Genomics
Behavioral Sciences
Biological Techniques
Biomedicine
Brain
Brain - immunology
Brain - metabolism
Databases, Genetic
etiology
Genetic
Genetic aspects
Genetic Predisposition to Disease
Genetic Predisposition to Disease - genetics
genetics
Genome-Wide Association Study
Genome-Wide Association Study - methods
Genomics
Histones
Histones - genetics
Histones - metabolism
Humans
immunology
Life Sciences
Mental Disorders
Mental Disorders - etiology
Mental Disorders - genetics
Mental illness
metabolism
methods
Methylation
Neurobiology
Neurons and Cognition
Neurosciences
Physiological aspects
Psychiatry
Psykiatri
Risk factors
Signal Transduction
Signal Transduction - genetics
United States
Schizophrenia
Depression
Genome-wide association studies
Statistical methods
Online AccessGet full text

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Abstract Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them. 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.
AbstractList 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.
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.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.
Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them. 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.
Audience Academic
Author Cormand Rifà, Bru
Psychiatric Genomics Consortium
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Witte, John S
Cuccaro, Michael L
Duketis, Eftichia
Choudhury, Khalid
Dawson, Geraldine
Perlis, Roy H
Etain, Bruno
Akil, Hu
Universitat de Barcelona
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COPYRIGHT 2015 Nature Publishing Group
(c) Cormand Rifà, Bru, 2015 info:eu-repo/semantics/openAccess
Distributed under a Creative Commons Attribution 4.0 International License
2015 Nature America, Inc. All rights reserved. 2015
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– notice: 2015 Nature America, Inc. All rights reserved. 2015
CorporateAuthor The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium
Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium
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Issue 2
Keywords Schizophrenia
Depression
Genome-wide association studies
Statistical methods
Language English
License Distributed under a Creative Commons Attribution 4.0 International License: http://creativecommons.org/licenses/by/4.0
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Snippet Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take...
Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are...
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SubjectTerms 631/114/2415
631/208/205/2138
631/378/1689/1414
631/378/1689/1799
Animal Genetics and Genomics
Behavioral Sciences
Biological Techniques
Biomedicine
Brain
Brain - immunology
Brain - metabolism
Databases, Genetic
etiology
Genetic
Genetic aspects
Genetic Predisposition to Disease
Genetic Predisposition to Disease - genetics
genetics
Genome-Wide Association Study
Genome-Wide Association Study - methods
Genomics
Histones
Histones - genetics
Histones - metabolism
Humans
immunology
Life Sciences
Mental Disorders
Mental Disorders - etiology
Mental Disorders - genetics
Mental illness
metabolism
methods
Methylation
Neurobiology
Neurons and Cognition
Neurosciences
Physiological aspects
Psychiatry
Psykiatri
Risk factors
Signal Transduction
Signal Transduction - genetics
Title Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
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https://pubmed.ncbi.nlm.nih.gov/PMC4378867
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Volume 18
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