The University of Southampton
University of Southampton Institutional Repository

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

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
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.
1097-6256
199-209
O'Dushlaine, Colm
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Wienker, Thomas F
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Wijsman, Ellen M
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Witt, Stephanie H
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Xu, Wei
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Young, Allan H
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Zammit, Stanley
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Kelsoe, John R
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Sklar, Pamela
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Daly, Mark J
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O'Donovan, Michael C
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Craddock, Nicholas
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Kendler, Kenneth S
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A Weiss, Lauren
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Wray, Naomi R
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Zhao, Zhaoming
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Geschwind, Daniel H
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Sullivan, Patrick F
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O'Dushlaine, Colm, Rossin, Lizzy and Lee, Phil H et al. (2015) Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nature Neuroscience, 18 (2), 199-209. (doi:10.1038/nn.3922). (PMID:25599223)

Record type: Article

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.

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Accepted/In Press date: 10 December 2014
e-pub ahead of print date: 19 January 2015
Published date: 2015
Organisations: Clinical Neuroscience

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Local EPrints ID: 375565
URI: http://eprints.soton.ac.uk/id/eprint/375565
ISSN: 1097-6256
PURE UUID: a441ed09-4000-4d51-aa25-57bf06a7253a

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Date deposited: 31 Mar 2015 08:56
Last modified: 14 Mar 2024 19:28

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Author: Colm O'Dushlaine
Author: Lizzy Rossin
Author: Phil H Lee
Author: Laramie Duncan
Author: Neelroop N Parikshak
Author: Stephen Newhouse
Author: Stephan Ripke
Author: Benjamin M Neale
Author: Shaun M Purcell
Author: Danielle Posthuma
Author: John I Nurnberger
Author: S Hong Lee
Author: Stephen V Faraone
Author: Roy H Perlis
Author: Bryan J Mowry
Author: Anita Thapar
Author: Michael E Goddard
Author: John S Witte
Author: Devin Absher
Author: Ingrid Agartz
Author: Huda Akil
Author: Farooq Amin
Author: Ole A. Andreassen
Author: Adebayo Anjorin
Author: Richard Anney
Author: Verneri Anttila
Author: Dan E. Arking
Author: Philip Asherson
Author: Maria H. Azevedo
Author: Lena Backlund
Author: Judith A. Badner
Author: Anthony J. Bailey
Author: Tobias Banaschewski
Author: Jack D. Barchas
Author: Michael R. Barnes
Author: Thomas B. Barrett
Author: Nicholas Bass
Author: Agatino Battaglia
Author: Michael Bauer
Author: Mònica Bayés
Author: Frank Bellivier
Author: Sarah E. Bergen
Author: Wade Berrettini
Author: Catalina Betancur
Author: Thomas Bettecken
Author: Joseph Biederman
Author: Elisabeth B. Binder
Author: Donald W. Black
Author: Douglas H.R. Blackwood
Author: Cinnamon S. Bloss
Author: Michael Boehnke
Author: Dorret I. Boomsma
Author: René Breuer
Author: Richard Bruggeman
Author: Paul Cormican
Author: Nancy G Buccola
Author: Jan K Buitelaar
Author: William E Bunney
Author: Joseph D Buxbaum
Author: William F Byerley
Author: Enda M Byrne
Author: Sian Caesar
Author: Wiepke Cahn
Author: Rita M Cantor
Author: Miguel Casas
Author: Aravinda Chakravarti
Author: Kimberly Chambert
Author: Khalid Choudhury
Author: Sven Cichon
Author: Manuel Mattheisen
Author: C Robert Cloninger
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Author: Edwin H Cook
Author: Hilary Coon
Author: Bru Cormand
Author: Aiden Corvin
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Author: David W Craig
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Author: Jennifer Crosbie
Author: Michael L Cuccaro
Author: David Curtis
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Author: Susmita Datta
Author: Geraldine Dawson
Author: Richard Day
Author: Eco J De Geus
Author: Franziska Degenhardt
Author: Srdjan Djurovic
Author: Gary J Donohoe
Author: Alysa E Doyle
Author: Jubao Duan
Author: Frank Dudbridge
Author: Eftichia Duketis
Author: Richard P Ebstein
Author: Howard J Edenberg
Author: Josephine Elia
Author: Sean Ennis
Author: Bruno Etain
Author: Ayman Fanous
Author: Anne E Farmer
Author: I Nicol Ferrier
Author: Matthew Flickinger
Author: Eric Fombonne
Author: Tatiana Foroud
Author: Josef Frank
Author: Barbara Franke
Author: Christine Fraser
Author: Robert Freedman
Author: Nelson B Freimer
Author: Christine M Freitag
Author: Marion Friedl
Author: Louise Frisén
Author: Louise Gallagher
Author: Pablo V Gejman
Author: Lyudmila Georgieva
Author: Elliot S Gershon
Author: Ina Giegling
Author: Michael Gill
Author: Scott D Gordon
Author: Katherine Gordon-Smith
Author: Elaine K Green
Author: Tiffany A Greenwood
Author: Dorothy E Grice
Author: Magdalena Gross
Author: Detelina Grozeva
Author: Weihua Guan
Author: Hugh Gurling
Author: Lieuwe De Haan
Author: Jonathan L Haines
Author: Hakon Hakonarson
Author: Joachim Hallmayer
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Author: Thomas F Hansen
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