Genetic correlation between amyotrophic lateral sclerosis and schizophrenia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-03-21

AUTHORS

Russell L. McLaughlin, Dick Schijven, Wouter van Rheenen, Kristel R. van Eijk, Margaret O’Brien, René S. Kahn, Roel A. Ophoff, An Goris, Daniel G. Bradley, Ammar Al-Chalabi, Leonard H. van den Berg, Jurjen J. Luykx, Orla Hardiman, Jan H. Veldink, Project MinE GWAS Consortium, Aleksey Shatunov, Annelot M. Dekker, Frank P. Diekstra, Sara L. Pulit, Rick A. A. van der Spek, Perry T. C. van Doormaal, William Sproviero, Ashley R. Jones, Garth A. Nicholson, Dominic B. Rowe, Roger Pamphlett, Matthew C. Kiernan, Denis Bauer, Tim Kahlke, Kelly Williams, Filip Eftimov, Isabella Fogh, Nicola Ticozzi, Kuang Lin, Stéphanie Millecamps, François Salachas, Vincent Meininger, Mamede de Carvalho, Susana Pinto, Jesus S. Mora, Ricardo Rojas-García, Meraida Polak, Siddharthan Chandran, Shuna Colville, Robert Swingler, Karen E. Morrison, Pamela J. Shaw, John Hardy, Richard W. Orrell, Alan Pittman, Katie Sidle, Pietro Fratta, Andrea Malaspina, Susanne Petri, Susanna Abdulla, Carsten Drepper, Michael Sendtner, Thomas Meyer, Martina Wiedau-Pazos, Catherine Lomen-Hoerth, Vivianna M. Van Deerlin, John Q. Trojanowski, Lauren Elman, Leo McCluskey, Nazli Basak, Thomas Meitinger, Peter Lichtner, Milena Blagojevic-Radivojkov, Christian R. Andres, Cindy Maurel, Gilbert Bensimon, Bernhard Landwehrmeyer, Alexis Brice, Christine A. M. Payan, Safa Saker-Delye, Alexandra Dürr, Nicholas Wood, Lukas Tittmann, Wolfgang Lieb, Andre Franke, Marcella Rietschel, Sven Cichon, Markus M. Nöuthen, Philippe Amouyel, Christophe Tzourio, Jean- François Dartigues, Andre G. Uitterlinden, Fernando Rivadeneira, Karol Estrada, Albert Hofman, Charles Curtis, Anneke J. van der Kooi, Marianne de Visser, Markus Weber, Christopher E. Shaw, Bradley N. Smith, Orietta Pansarasa, Cristina Cereda, Roberto Del Bo, Giacomo P. Comi, Sandra D’Alfonso, Cinzia Bertolin, Gianni Sorarù, Letizia Mazzini, Viviana Pensato, Cinzia Gellera, Cinzia Tiloca, Antonia Ratti, Andrea Calvo, Cristina Moglia, Maura Brunetti, Simon Arcuti, Rosa Capozzo, Chiara Zecca, Christian Lunetta, Silvana Penco, Nilo Riva, Alessandro Padovani, Massimiliano Filosto, Ian Blair, P Nigel Leigh, Federico Casale, Adriano Chio, Ettore Beghi, Elisabetta Pupillo, Rosanna Tortelli, Giancarlo Logroscino, John Powell, Albert C. Ludolph, Jochen H. Weishaupt, Wim Robberecht, Philip Van Damme, Robert H. Brown, Jonathan Glass, John E. Landers, Peter M. Andersen, Philippe Corcia, Patrick Vourc'h, Vincenzo Silani, Michael A. van Es, R Jeroen Pasterkamp, Cathryn M. Lewis, Gerome Breen, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T. R. 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 C. K. Chan, Ronald Y. L. Chan, Eric Y. H. Chen, Wei Cheng, Eric F. C. 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, 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 K. E. 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, 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 H. M. 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 H. R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, 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, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, 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

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies. More... »

PAGES

14774

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    N/A

    VOLUME

    8

    Author Affiliations

  • Trinity College Dublin
  • University Medical Center Utrecht
  • University of California Los Angeles
  • KU Leuven
  • King's College London
  • Macquarie University
  • University of Sydney
  • Commonwealth Scientific and Industrial Research Organisation
  • Academic Medical Center
  • Istituto Auxologico Italiano
  • University of Milan
  • Institut du Cerveau et de la Moelle Épinière
  • Centro Hospitalar Lisboa Norte
  • Carlos III Hospital
  • Emory University
  • University of Edinburgh
  • Queen Elizabeth Hospital Birmingham
  • University of Sheffield
  • University College London
  • Queen Mary University of London
  • Hannover Medical School
  • Otto-von-Guericke University Magdeburg
  • University of Würzburg
  • University of California, San Francisco
  • University of Pennsylvania
  • Boğaziçi University
  • François Rabelais University
  • Pitié-Salpêtrière Hospital
  • University of Ulm
  • Sorbonne University
  • Genethon (France)
  • Kiel University
  • Central Institute of Mental Health
  • Forschungszentrum Jülich
  • University of Bonn
  • Erasmus University Medical Center
  • Kantonsspital St. Gallen
  • Fondazione Istituto Neurologico Nazionale Casimiro Mondino
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • University of Genoa
  • University of Padua
  • University of Eastern Piedmont Amadeo Avogadro
  • Istituto Neurologico Carlo Besta
  • Azienda Ospedaliera Citta' Della Salute E Della Scienza Di Torino
  • Ospedale Niguarda Ca' Granda
  • San Raffaele Hospital
  • Spedali Civili di Brescia
  • University of Sussex
  • University of Turin
  • Mario Negri Institute for Pharmacological Research
  • University of Bari Aldo Moro
  • Universitaire Ziekenhuizen Leuven
  • University of Massachusetts Medical School
  • Umeå University
  • Centre Hospitalier Universitaire de Tours
  • Broad Institute
  • Massachusetts General Hospital
  • Cardiff University
  • Boston Children's Hospital
  • Diakonhjemmet Hospital
  • Lundbeck Foundation
  • Stanford 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
  • Icahn School of Medicine at Mount Sinai
  • 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)
  • Sheba Medical Center
  • 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
  • Roche (Switzerland)
  • Washington DC VA Medical Center
  • Heidelberg University
  • University of Colorado Anschutz Medical Campus
  • Martin Luther University Halle-Wittenberg
  • Ludwig Maximilian University of Munich
  • Department of Medical Sciences
  • University of Queensland
  • Illumina (United States)
  • Mental Health Services
  • 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
  • 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)
  • 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
  • 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/ncomms14774

    DOI

    http://dx.doi.org/10.1038/ncomms14774

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084128985

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28322246


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