Manuel Mattheisen

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Colm O'Dushlaine, Regeneron Pharmaceut Inc, Regeneron Genet Ctr, United States
  • Lizzy Rossin, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res, United States
  • Phil H. Lee, Harvard University, United States
  • Laramie Duncan, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res, Unknown
  • Neelroop N. Parikshak, Univ Calif Los Angeles, University of California Los Angeles, University of California System, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Unknown
  • Stephen Newhouse, Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, MRC, Unknown
  • Stephan Ripke, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res, United States
  • Benjamin M. Neale, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res, United States
  • Shaun M. Purcell, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res, United States
  • Danielle Posthuma, Vrije Univ Amsterdam, VU University Amsterdam, Dept Funct Gen, Netherlands
  • John I. Nurnberger, Indiana Univ, Indiana University System, Indiana University-Purdue University Indianapolis, Sch Med, Inst Psychiat Res, United States
  • S. Hong Lee, Univ Queensland, University of Queensland, Queensland Brain Inst, Australia
  • Stephen V. Faraone, SUNY Upstate Med Univ, State University of New York (SUNY) System, State University of New York (SUNY) Upstate Medical Center, Dept Psychiat, United States
  • Roy H. Perlis, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res, United States
  • Bryan J. Mowry, Univ Queensland, University of Queensland, Queensland Brain Inst, Australia
  • Anita Thapar, Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Gen
  • ,
  • Michael E. Goddard, Dept Environm & Primary Ind Victoria, Biosci Res Div, Australia
  • John S. Witte, Univ Calif San Francisco, University of California San Francisco, University of California System, Dept Epidemiol & Biostat, United States
  • Devin Absher, HudsonAlpha Inst Biotechnol, United States
  • Ingrid Agartz, Univ Oslo, University of Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Norway
  • Huda Akil, Univ Michigan, University of Michigan, University of Michigan System, Mol & Behav Neurosci Inst, Mol Psychiat Lab, United States
  • Farooq Amin, Emory Univ, Emory University, Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, United States
  • Ole A. Andreassen, Univ Oslo, University of Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Norway
  • Adebayo Anjorin, UCL, University College London, University of London, Mental Hlth Sci Unit
  • ,
  • Richard Anney, Trin Coll Dublin, Trinity College Dublin, Dept Psychiat, Ireland
  • Verneri Anttila, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res, United States
  • Dan E. Arking, Johns Hopkins Univ, Johns Hopkins University, Sch Med, McKusick Nathans Inst Genet Med, United States
  • Philip Asherson, Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, MRC
  • ,
  • Maria H. Azevedo, Univ Coimbra, Universidade de Coimbra, Fac Med, Portugal
  • Lena Backlund, Karolinska Inst, Karolinska Institutet, Ctr Mol Med, Dept Mol Med & Surg, Sweden
  • Judith A. Badner, Univ Chicago, University of Chicago, Dept Psychiat, United States
  • Anthony J. Bailey, Univ British Columbia, University of British Columbia, Dept Psychiat, Canada
  • Tobias Banaschewski, Heidelberg Univ, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherary, Germany
  • Jack D. Barchas, Cornell Univ, Cornell University, Weill Med Coll, Dept Psychiat, United States
  • Michael R. Barnes, GlaxoSmithKline
  • ,
  • Thomas B. Barrett, Portland VA Med Ctr, Portland VA Medical Center, US Department of Veteran Affairs, United States
  • Nicholas Bass, UCL, University College London, University of London, Mental Hlth Sci Unit
  • ,
  • Agatino Battaglia, Stella Maris Inst Child & Adolescent Neuropsychia, Italy
  • Michael Bauer, Carl Gustav Carus Univ Hosp, CARL GUSTAV CARUS UNIVERSITY HOSPITAL, Dresden University of Technology, Dept Psychiat & Psychotherapy, Germany
  • Monica Bayes, CNAG, PCB, Spain
  • Frank Bellivier, INSERM, Institut National de la Sante et de la Recherche Medicale (Inserm), U955, France
  • Sarah E. Bergen, Harvard University, United States
  • Wade Berrettini, Univ Penn, University of Pennsylvania, Dept Psychiat, United States
  • Catalina Betancur, INSERM, Institut National de la Sante et de la Recherche Medicale (Inserm), U952, France
  • Thomas Bettecken, Max Planck Inst Psychiat, Max Planck Society, Germany
  • Joseph Biederman, Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & ADHD, United States
  • Elisabeth B. Binder, Max Planck Inst Psychiat, Max Planck Society, Germany
  • Donald W. Black, Univ Iowa, University of Iowa, Dept Psychiat, United States
  • Manuel Mattheisen
  • Sandra Meier, Heidelberg Univ, Ruprecht Karl University Heidelberg, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Denmark
  • IIBDGC
  • ,
  • Network & Pathway Anal Subgrp Psyc

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 languageEnglish
JournalNature Neuroscience
Volume18
Issue2
Pages (from-to)199-209
Number of pages11
ISSN1097-6256
DOIs
Publication statusPublished - Feb 2015

    Research areas

  • DE-NOVO MUTATIONS, SCHIZOPHRENIA, METHYLATION, DISORDERS, AUTISM, BRAIN, PROMOTERS, BURDEN, LOCI

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