Biological insights from 108 schizophrenia-associated genetic loci View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-07

AUTHORS

, Stephan Ripke, Benjamin M Neale, Aiden Corvin, James TR Walters, Kai-How Farh, Peter A Holmans, Phil Lee, Brendan Bulik-Sullivan, David A Collier, Hailiang Huang, Tune H Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A Bacanu, Martin Begemann, Richard A Belliveau, Judit Bene, Sarah E Bergen, Elizabeth Bevilacqua, Tim B Bigdeli, Donald W Black, Richard Bruggeman, Nancy G Buccola, Randy L Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M Cantor, Vaughan J Carr, Noa Carrera, Stanley V Catts, Kimberley D Chambert, Raymond CK Chan, Ronald YL Chan, Eric YH Chen, Wei Cheng, Eric FC Cheung, Siow Ann Chong, C Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J Crowley, David Curtis, Michael Davidson, Kenneth L Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H Fanous, Martilias S Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B Freimer, Marion Friedl, Joseph I Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M Hartmann, Frans A Henskens, Stefan Herms, Joel N Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V Hollegaard, David M Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C Keller, James L Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K Kähler, Claudine Laurent, Jimmy Lee, S Hong Lee, Sophie E Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik KE Magnusson, Brion S Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W McCarley, Colm McDonald, Andrew M McIntosh, Sandra Meier, Carin J Meijer, Bela Melegh, Ingrid Melle, Raquelle I Mesholam-Gately, Andres Metspalu, Patricia T Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W Morris, Ole Mors, Kieran C Murphy, Robin M Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A Nertney, Gerald Nestadt, Kristin K Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, , Christos Pantelis, George N Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J Pocklington, John Powell, Alkes Price, Ann E Pulver, Shaun M Purcell, Digby Quested, Henrik B Rasmussen, Abraham Reichenberg, Mark A Reimers, Alexander L Richards, Joshua L Roffman, Panos Roussos, Douglas M Ruderfer, Veikko Salomaa, Alan R Sanders, Ulrich Schall, Christian R Schubert, Thomas G Schulze, Sibylle G Schwab, Edward M Scolnick, Rodney J Scott, Larry J Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M Silverman, Kang Sim, Petr Slominsky, Jordan W Smoller, Hon-Cheong So, Chris C A Spencer, Eli A Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E Straub, Eric Strengman, Jana Strohmaier, T Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M Svrakic, Jin P Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T Webb, Mark Weiser, Dieter B Wildenauer, Nigel M Williams, Stephanie Williams, Stephanie H Witt, Aaron R Wolen, Emily HM Wong, Brandon K Wormley, Hualin Simon Xi, Clement C Zai, Xuebin Zheng, Fritz Zimprich, Naomi R Wray, Kari Stefansson, Peter M Visscher, , Rolf Adolfsson, Ole A Andreassen, Douglas HR Blackwood, Elvira Bramon, Joseph D Buxbaum, Anders D Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V Gejman, Michael Gill, Hugh Gurling, Christina M Hultman, Nakao Iwata, Assen V Jablensky, Erik G Jönsson, Kenneth S Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F Levinson, Qingqin S Li, Jianjun Liu, Anil K Malhotra, Steven A McCarroll, Andrew McQuillin, Jennifer L Moran, Preben B Mortensen, Bryan J Mowry, Markus M Nöthen, Roel A Ophoff, Michael J Owen, Aarno Palotie, Carlos N Pato, Tracey L Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P Riley, Dan Rujescu, Pak C Sham, Pamela Sklar, David St Clair, Daniel R Weinberger, Jens R Wendland, Thomas Werge, Mark J Daly, Patrick F Sullivan, Michael C O’Donovan

ABSTRACT

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia. More... »

PAGES

421

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  • Journal

    TITLE

    Nature

    ISSUE

    7510

    VOLUME

    511

    Author Affiliations

  • Broad Institute
  • Massachusetts General Hospital
  • Trinity College Dublin
  • Cardiff University
  • King's College London
  • Boston Children's Hospital
  • Diakonhjemmet Hospital
  • Lundbeck Foundation
  • Stanford University
  • Emory University
  • Virginia Commonwealth University
  • Max Planck Institute for Experimental Medicine
  • University of Pecs
  • Karolinska Institute
  • University of Iowa
  • Louisiana State University Health Sciences Center New Orleans
  • University of California, San Francisco
  • University Medical Center Utrecht
  • Icahn School of Medicine at Mount Sinai
  • University of California Los Angeles
  • UNSW Australia
  • Schizophrenia Research Institute
  • Institute of Psychology
  • University of Hong Kong
  • University of North Carolina at Chapel Hill
  • Castle Peak Hospital
  • Institute of Mental Health
  • Washington University in St. Louis
  • New Sorbonne University
  • Janssen (United States)
  • University College London
  • Sheba Medical Center
  • University of Bonn
  • University of Antwerp
  • Aarhus University
  • National and Kapodistrian University of Athens
  • University College Cork
  • Oslo University Hospital
  • National University of Ireland, Galway
  • NorthShore University HealthSystem
  • London School of Hygiene & Tropical Medicine
  • PHI University Psychiatric Clinic - Skopje
  • University of Regensburg
  • National Institute for Health and Welfare
  • Washington DC VA Medical Center
  • Heidelberg University
  • University of Colorado Anschutz Medical Campus
  • Martin Luther University Halle-Wittenberg
  • Ludwig Maximilian University of Munich
  • Pitié-Salpêtrière Hospital
  • Department of Medical Sciences
  • University of Queensland
  • Academic Medical Center
  • Illumina (United States)
  • University of Newcastle Australia
  • University of Basel
  • Harvard University
  • Statens Serum Institut
  • Fujita Health University
  • Stavanger University Hospital
  • Vall d'Hebron Research Institute
  • University of Western Australia
  • Medical University of Sofia
  • University of Colorado Boulder
  • University of Toronto
  • Institute of Molecular Genetics
  • Latvian Biomedical Research and Study Centre
  • University of Southern California
  • Vilnius University
  • Charles University
  • Duke NUS Graduate Medical School
  • Hadassah Medical Center
  • Johns Hopkins University
  • Columbia University
  • Pomeranian Medical University
  • Sørlandet Sykehus
  • VA Boston Healthcare System
  • University of Edinburgh
  • Beth Israel Deaconess Medical Center
  • University of Tartu
  • Eli Lilly (United Kingdom)
  • Aarhus University Hospital
  • Royal College of Surgeons in Ireland
  • Maastricht University Medical Centre
  • Munich Cluster for Systems Neurology
  • Jena University Hospital
  • Eli Lilly (United States)
  • Umeå University
  • Queen's University Belfast
  • University of California, Berkeley
  • Melbourne Health
  • University of Belgrade
  • University of North Carolina System
  • Institute for Molecular Medicine Finland
  • University of Oxford
  • Pfizer (United States)
  • University of Göttingen
  • University of Erlangen-Nuremberg
  • National Cancer Institute
  • Tbilisi State Medical University
  • James J Peters VA Medical Center
  • Wellcome Centre for Human Genetics
  • deCODE Genetics (Iceland)
  • Medical University of Vienna
  • Lieber Institute for Brain Development
  • Berkshire Healthcare NHS Foundation Trust
  • University of Verona
  • Oulu University Hospital
  • Health Research Board
  • Queen Elizabeth II Medical Centre
  • Genome Institute of Singapore
  • Forschungszentrum Jülich
  • Hebrew University of Jerusalem
  • Zucker Hillside Hospital
  • National University of Singapore
  • Amsterdam Neuroscience
  • University of Aberdeen
  • University of Copenhagen
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature13595

    DOI

    http://dx.doi.org/10.1038/nature13595

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1021916306

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25056061


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