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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-02

AUTHORS

The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium, Colm O'Dushlaine, Lizzy Rossin, Phil H Lee, Laramie Duncan, Neelroop N Parikshak, Stephen Newhouse, Stephan Ripke, Benjamin M Neale, Shaun M Purcell, Danielle Posthuma, John I Nurnberger, S Hong Lee, Stephen V Faraone, Roy H Perlis, Bryan J Mowry, Anita Thapar, Michael E Goddard, John S Witte, Devin Absher, Ingrid Agartz, Huda Akil, Farooq Amin, Ole A Andreassen, Adebayo Anjorin, Richard Anney, Verneri Anttila, Dan E Arking, Philip Asherson, Maria H Azevedo, Lena Backlund, Judith A Badner, Anthony J Bailey, Tobias Banaschewski, Jack D Barchas, Michael R Barnes, Thomas B Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Mònica Bayés, Frank Bellivier, Sarah E Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B Binder, Donald W Black, Douglas H R Blackwood, Cinnamon S Bloss, Michael Boehnke, Dorret I Boomsma, René Breuer, Richard Bruggeman, Paul Cormican, Nancy G Buccola, Jan K Buitelaar, William E Bunney, Joseph D Buxbaum, William F Byerley, Enda M Byrne, Sian Caesar, Wiepke Cahn, Rita M Cantor, Miguel Casas, Aravinda Chakravarti, Kimberly Chambert, Khalid Choudhury, Sven Cichon, Manuel Mattheisen, C Robert Cloninger, David A Collier, Edwin H Cook, Hilary Coon, Bru Cormand, Aiden Corvin, William H Coryell, David W Craig, Ian W Craig, Jennifer Crosbie, Michael L Cuccaro, David Curtis, Darina Czamara, Susmita Datta, Geraldine Dawson, Richard Day, Eco J De Geus, Franziska Degenhardt, Srdjan Djurovic, Gary J Donohoe, Alysa E Doyle, Jubao Duan, Frank Dudbridge, Eftichia Duketis, Richard P Ebstein, Howard J Edenberg, Josephine Elia, Sean Ennis, Bruno Etain, Ayman Fanous, Anne E Farmer, I Nicol Ferrier, Matthew Flickinger, Eric Fombonne, Tatiana Foroud, Josef Frank, Barbara Franke, Christine Fraser, Robert Freedman, Nelson B Freimer, Christine M Freitag, Marion Friedl, Louise Frisén, Louise Gallagher, Pablo V Gejman, Lyudmila Georgieva, Elliot S Gershon, Ina Giegling, Michael Gill, Scott D Gordon, Katherine Gordon-Smith, Elaine K Green, Tiffany A Greenwood, Dorothy E Grice, Magdalena Gross, Detelina Grozeva, Weihua Guan, Hugh Gurling, Lieuwe De Haan, Jonathan L Haines, Hakon Hakonarson, Joachim Hallmayer, Steven P Hamilton, Marian L Hamshere, Thomas F Hansen, Annette M Hartmann, Martin Hautzinger, Andrew C Heath, Anjali K Henders, Stefan Herms, Ian B Hickie, Maria Hipolito, Susanne Hoefels, Florian Holsboer, Witte J Hoogendijk, Jouke-Jan Hottenga, Christina M Hultman, Vanessa Hus, Andrés Ingason, Marcus Ising, Stéphane Jamain, Edward G Jones, Ian Jones, Lisa Jones, Jung-Ying Tzeng, Anna K Kähler, René S Kahn, Radhika Kandaswamy, Matthew C Keller, James L Kennedy, Elaine Kenny, Lindsey Kent, Yunjung Kim, George K Kirov, Sabine M Klauck, Lambertus Klei, James A Knowles, Martin A Kohli, Daniel L Koller, Bettina Konte, Ania Korszun, Lydia Krabbendam, Robert Krasucki, Jonna Kuntsi, Phoenix Kwan, Mikael Landén, Niklas Längström, Mark Lathrop, Jacob Lawrence, William B Lawson, Marion Leboyer, David H Ledbetter, Todd Lencz, Klaus-Peter Lesch, Douglas F Levinson, Cathryn M Lewis, Jun Li, Paul Lichtenstein, Jeffrey A Lieberman, Dan-Yu Lin, Don H Linszen, Chunyu Liu, Falk W Lohoff, Sandra K Loo, Catherine Lord, Jennifer K Lowe, Susanne Lucae, Donald J MacIntyre, Pamela A F Madden, Elena Maestrini, Patrik K E Magnusson, Pamela B Mahon, Wolfgang Maier, Anil K Malhotra, Shrikant M Mane, Christa L Martin, Nicholas G Martin, Keith Matthews, Morten Mattingsdal, Steven A McCarroll, Kevin A McGhee, James J McGough, Patrick J McGrath, Peter McGuffin, Melvin G McInnis, Andrew McIntosh, Rebecca McKinney, Alan W McLean, Francis J McMahon, William M McMahon, Andrew McQuillin, Helena Medeiros, Sarah E Medland, Sandra Meier, Ingrid Melle, Fan Meng, Jobst Meyer, Christel M Middeldorp, Lefkos Middleton, Vihra Milanova, Ana Miranda, Anthony P Monaco, Grant W Montgomery, Jennifer L Moran, Daniel Moreno-De-Luca, Gunnar Morken, Derek W Morris, Eric M Morrow, Valentina Moskvina, Pierandrea Muglia, Thomas W Mühleisen, Walter J Muir, Bertram Müller-Myhsok, Michael Murtha, Richard M Myers, Inez Myin-Germeys, Michael C Neale, Stan F Nelson, Caroline M Nievergelt, Ivan Nikolov, Vishwajit Nimgaonkar, Willem A Nolen, Markus M Nöthen, Evaristus A Nwulia, Dale R Nyholt, Robert D Oades, Ann Olincy, Guiomar Oliveira, Line Olsen, Roel A Ophoff, Urban Osby, Michael J Owen, Aarno Palotie, Jeremy R Parr, Andrew D Paterson, Carlos N Pato, Michele T Pato, Brenda W Penninx, Michele L Pergadia, Margaret A Pericak-Vance, Benjamin S Pickard, Jonathan Pimm, Joseph Piven, James B Potash, Fritz Poustka, Peter Propping, Vinay Puri, Digby J Quested, Emma M Quinn, Josep Antoni Ramos-Quiroga, Henrik B Rasmussen, Soumya Raychaudhuri, Karola Rehnström, Andreas Reif, Marta Ribasés, John P Rice, Marcella Rietschel, Kathryn Roeder, Herbert Roeyers, Aribert Rothenberger, Guy Rouleau, Douglas Ruderfer, Dan Rujescu, Alan R Sanders, Stephan J Sanders, Susan L Santangelo, Joseph A Sergeant, Russell Schachar, Martin Schalling, Alan F Schatzberg, William A Scheftner, Gerard D Schellenberg, Stephen W Scherer, Nicholas J Schork, Thomas G Schulze, Johannes Schumacher, Markus Schwarz, Edward Scolnick, Laura J Scott, Jianxin Shi, Paul D Shilling, Stanley I Shyn, Jeremy M Silverman, Susan L Slager, Susan L Smalley, Johannes H Smit, Erin N Smith, Edmund J S Sonuga-Barke, David St. Clair, Matthew State, Michael Steffens, Hans-Christoph Steinhausen, John S Strauss, Jana Strohmaier, T Scott Stroup, James S Sutcliffe, Peter Szatmari, Szabocls Szelinger, Srinivasa Thirumalai, Robert C Thompson, Alexandre A Todorov, Federica Tozzi, Jens Treutlein, Manfred Uhr, Edwin J C G van den Oord, Gerard Van Grootheest, Jim Van Os, Astrid M Vicente, Veronica J Vieland, John B Vincent, Peter M Visscher, Christopher A Walsh, Thomas H Wassink, Stanley J Watson, Myrna M Weissman, Thomas Werge, Thomas F Wienker, Ellen M Wijsman, Gonneke Willemsen, Nigel Williams, A Jeremy Willsey, Stephanie H Witt, Wei Xu, Allan H Young, Timothy W Yu, Stanley Zammit, Peter P Zandi, Peng Zhang, Frans G Zitman, Sebastian Zöllner, Bernie Devlin, John R Kelsoe, Pamela Sklar, Mark J Daly, Michael C O'Donovan, Nicholas Craddock, Kenneth S Kendler, Lauren A Weiss, Naomi R Wray, Zhongming Zhao, Daniel H Geschwind, Patrick F Sullivan, Jordan W Smoller, Peter A Holmans, Gerome Breen

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. More... »

PAGES

199-209

References to SciGraph publications

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  • Journal

    TITLE

    Nature Neuroscience

    ISSUE

    2

    VOLUME

    18

    Author Affiliations

  • Broad Institute
  • Massachusetts General Hospital
  • University of California Los Angeles
  • National Institute for Health Research
  • Icahn School of Medicine at Mount Sinai
  • Erasmus University Medical Center
  • Indiana University – Purdue University Indianapolis
  • University of Queensland
  • SUNY Upstate Medical University
  • Queensland Centre for Mental Health Research
  • Cardiff University
  • University of Melbourne
  • University of California, San Francisco
  • HudsonAlpha Institute for Biotechnology
  • Diakonhjemmet Hospital
  • University of Michigan–Ann Arbor
  • Emory University
  • Oslo University Hospital
  • University College London
  • Trinity College Dublin
  • Johns Hopkins University
  • King's College London
  • University of Coimbra
  • Karolinska Institute
  • University of Chicago
  • University of British Columbia
  • Central Institute of Mental Health
  • Cornell University
  • GlaxoSmithKline (United Kingdom)
  • Portland VA Medical Center
  • University Hospital Carl Gustav Carus
  • Centro Nacional de Análisis Genómico
  • Fondation FondaMental
  • University of Pennsylvania
  • Sorbonne University
  • Max Planck Institute of Psychiatry
  • Harvard University
  • University of Iowa
  • University of Edinburgh
  • Scripps Health
  • Amsterdam Neuroscience
  • Louisiana State University Health Sciences Center New Orleans
  • University of California, Irvine
  • Northern California Institute for Research and Education
  • University of Birmingham
  • University Medical Center Utrecht
  • Autonomous University of Barcelona
  • University of Basel
  • University of Bonn
  • Washington University in St. Louis
  • University of Illinois at Chicago
  • University of Utah
  • University of Barcelona
  • Translational Genomics Research Institute
  • University of Toronto
  • University of Miami
  • Munich Cluster for Systems Neurology
  • University of North Carolina at Chapel Hill
  • London School of Hygiene & Tropical Medicine
  • Goethe University Frankfurt
  • National University of Singapore
  • Assistance Publique -Hopitaux De Paris
  • Virginia Commonwealth University
  • Newcastle University
  • Oregon Health & Science University
  • University of Colorado Anschutz Medical Campus
  • Martin Luther University Halle-Wittenberg
  • QIMR Berghofer Medical Research Institute
  • Plymouth University
  • University of California, San Diego
  • University of Minnesota
  • Vanderbilt University Medical Center
  • Stanford University
  • University of Tübingen
  • University of Sydney
  • Howard University
  • North Carolina State University
  • University of Colorado System
  • Centre for Addiction and Mental Health
  • University of St Andrews
  • German Cancer Research Center
  • University of Pittsburgh
  • University of Southern California
  • Queen Mary University of London
  • Maastricht University Medical Centre
  • University of Gothenburg
  • Centre National de Génotypage
  • Geisinger Health System
  • Albert Einstein College of Medicine
  • Maastricht University
  • Academic Medical Center
  • University of Bologna
  • Sørlandet Sykehus
  • National Institute of Mental Health
  • University of Trier
  • Imperial College London
  • University of Valencia
  • Tufts University
  • Yale University
  • Norwegian University of Science and Technology
  • Brown University
  • University Medical Center Groningen
  • University of Duisburg-Essen
  • Hospitais da Universidade de Coimbra
  • Wellcome Sanger Institute
  • VU University Medical Center
  • University of Oxford
  • University of Würzburg
  • Vall d'Hebron Research Institute
  • Carnegie Mellon University
  • Ghent University
  • Universitätsmedizin Göttingen
  • McGill University
  • VU University Amsterdam
  • Rush University Medical Center
  • Hospital for Sick Children
  • Scripps Research Institute
  • University of Göttingen
  • National Cancer Institute
  • University of Washington
  • Mayo Clinic
  • University of Southampton
  • University of Aberdeen
  • Federal Institute for Drugs and Medical Devices
  • University of Zurich
  • Columbia University
  • Vanderbilt University
  • Oxford Health NHS Foundation Trust
  • Instituto Gulbenkian de Ciência
  • Nationwide Children's Hospital
  • University of Copenhagen
  • Leiden University Medical Center
  • VA San Diego Healthcare System
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nn.3922

    DOI

    http://dx.doi.org/10.1038/nn.3922

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1023495141

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25599223


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