Genetic correlation between amyotrophic lateral sclerosis and schizophrenia
Russell L. McLaughlin(Trinity College Dublin), Dick Schijven(University Medical Center Utrecht), Wouter van Rheenen(University Medical Center Utrecht), Kristel R. van Eijk(University Medical Center Utrecht), Margaret O’Brien(Trinity College Dublin), René S. Kahn(University Medical Center Utrecht), Roel A. Ophoff(University of California, Los Angeles), An Goris(VIB-KU Leuven Center for Brain & Disease Research), Daniel G. Bradley(Trinity College Dublin), Ammar Al‐Chalabi(King's College London), Leonard H. van den Berg(University Medical Center Utrecht), Jurjen J. Luykx(University Medical Center Utrecht), Orla Hardiman(Trinity College Dublin), Jan H. Veldink(University Medical Center Utrecht), Aleksey Shatunov(King's College London), Annelot M. Dekker(University Medical Center Utrecht), Frank P. Diekstra(University Medical Center Utrecht), Sara L. Pulit(University Medical Center Utrecht), Rick A. A. van der Spek(University Medical Center Utrecht), Perry T.C. van Doormaal(University Medical Center Utrecht), William Sproviero(King's College London), Ashley R. Jones(King's College London), Garth A. Nicholson(The University of Sydney), Dominic B. Rowe(Macquarie University), Roger Pamphlett(The University of Sydney), Matthew C. Kiernan(The University of Sydney), Denis C. Bauer(Commonwealth Scientific and Industrial Research Organisation), Tim Kahlke(Commonwealth Scientific and Industrial Research Organisation), Kelly L. Williams(Macquarie University), Filip Eftimov(Amsterdam UMC Location University of Amsterdam), Isabella Fogh(King's College London), Nicola Ticozzi(University of Milan), Kuang Lin(King's College London), Stéphanie Millecamps(Centre National de la Recherche Scientifique), François Salachas(Générale de Santé), Vincent Meininger(Générale de Santé), Mamede de Carvalho(University of Lisbon), Susana Pinto(University of Lisbon), Jesús S. Mora, Ricardo Rojas-García(Universitat Autònoma de Barcelona), Meraida Polak(Emory University), Siddharthan Chandran(Mott MacDonald (United Kingdom)), Shuna Colville(Mott MacDonald (United Kingdom)), Robert Swingler(Mott MacDonald (United Kingdom)), Karen Morrison(University Hospitals Birmingham NHS Foundation Trust), Pamela J. Shaw(University of Sheffield), John Hardy(University College London), Richard W. Orrell(University College London), Alan Pittman(Institute of Ophthalmology), Katie Sidle(University College London), Pietro Fratta(University College London), Andrea Malaspina(Motor Neurone Disease Association), Susanne Petri(Medizinische Hochschule Hannover), Susanna Abdulla(Otto-von-Guericke-Universität Magdeburg), Carsten Drepper(University of Würzburg), Michael Sendtner(University of Würzburg), Thomas Meyer(Humboldt-Universität zu Berlin), Martina Wiedau‐Pazos(University of California, Los Angeles), Catherine Lomen‐Hoerth(University of California, San Francisco), Vivianna M. Van Deerlin(University of Pennsylvania), John Q. Trojanowski(University of Pennsylvania), Lauren Elman(University of Pennsylvania), Leo McCluskey(University of Pennsylvania), Nazlı Başak(Boğaziçi University), Thomas Meitinger(Helmholtz Zentrum München), Peter Lichtner(Helmholtz Zentrum München), Milena Blagojevic-Radivojkov(Helmholtz Zentrum München), Christian Andrés(Université de Tours), Cindy Maurel(Université de Tours), Gilbert Bensimon(Sorbonne Université), G. Bernhard Landwehrmeyer(Universität Ulm), Alexis Brice(Centre National de la Recherche Scientifique), Christine Payan(Sorbonne Université), Safa Saker-Delye(Centre National de la Recherche Scientifique), Alexandra Dürr(Institut du Cerveau), Nicholas Wood(University College London), Lukas Tittmann(Christian-Albrechts-Universität zu Kiel), Wolfgang Lieb(Christian-Albrechts-Universität zu Kiel), André Franke(Christian-Albrechts-Universität zu Kiel), Marcella Rietschel(Heidelberg University), Sven Cichon(University of Bonn), Markus M. Nöuthen(University of Bonn), Philippe Amouyel(Inserm), Christophe Tzourio(Inserm), Jean François Dartigues(Inserm), André G. Uitterlinden(Erasmus MC), Fernando Rivadeneira(Erasmus MC), Karol Estrada(Erasmus MC), Albert Hofman(University of Bonn), Charles Curtis(King's College London), Anneke J. van der Kooi(Amsterdam UMC Location University of Amsterdam), Marianne de Visser(Amsterdam UMC Location University of Amsterdam), Markus Weber(Kantonsspital St. Gallen), Christopher E. Shaw(King's College London), Bradley Smith(King's College London), Orietta Pansarasa(Fondazione Istituto Neurologico Nazionale Casimiro Mondino), Cristina Cereda(Fondazione Istituto Neurologico Nazionale Casimiro Mondino), Roberto Del Bo(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico), Giacomo P. Comi(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico), Sandra D’Alfonso(Università degli Studi del Piemonte Orientale “Amedeo Avogadro”), Cinzia Bertolin(University of Padua), Gianni Sorarú(University of Padua), Letizia Mazzini(Università degli Studi del Piemonte Orientale “Amedeo Avogadro”), Viviana Pensato(Fondazione IRCCS Istituto Neurologico Carlo Besta), Cinzia Gellera(Fondazione IRCCS Istituto Neurologico Carlo Besta), Cinzia Tiloca(IRCCS Istituto Auxologico Italiano), Antonia Ratti(University of Milan), Andrea Calvo(Azienda Ospedaliera Citta' della Salute e della Scienza di Torino), Cristina Moglia(Azienda Ospedaliera Citta' della Salute e della Scienza di Torino), Maura Brunetti(Azienda Ospedaliera Citta' della Salute e della Scienza di Torino), Simon Arcuti(University of Bari Aldo Moro), Rosa Capozzo(University of Bari Aldo Moro), Chiara Zecca(University of Bari Aldo Moro), Christian Lunetta(Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico), Silvana Penco(Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda), Nilo Riva(Neuroscience Institute), Alessandro Padovani(Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia), Massimiliano Filosto(Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia), Ian P. Blair(Macquarie University), P. Nigel Leigh(Brighton and Sussex Medical School), Federico Casale(University of Turin), Adriano Chiò(Azienda Ospedaliera Citta' della Salute e della Scienza di Torino), Ettore Beghi(Mario Negri Institute for Pharmacological Research), Elisabetta Pupillo(Mario Negri Institute for Pharmacological Research), Rosanna Tortelli(University of Bari Aldo Moro), Giancarlo Logroscino(Ferioli & Gianotti (Italy)), John Powell(King's College London), Albert C. Ludolph(Universität Ulm), Jochen H. Weishaupt(Universität Ulm), Wim Robberecht(KU Leuven), Philip Van Damme(VIB-KU Leuven Center for Microbiology), Robert H. Brown(University of Massachusetts Chan Medical School), Jonathan D. Glass(Emory University), John E. Landers(University of Massachusetts Chan Medical School), Peter M. Andersen(Sorbonne Université), Philippe Corcia(Centre Hospitalier Universitaire de Tours), Patrick Vourc’h(Université de Tours), Vincenzo Silani(University of Milan), Michael A. van Es(University Medical Center Utrecht), R. Jeroen Pasterkamp(University Medical Center Utrecht), Cathryn M. Lewis(University Medical Center Groningen), Gerome Breen(University of California, Los Angeles), Stephan Ripke(Broad Institute), Benjamin M. Neale(Broad Institute), Aiden Corvin(Trinity College Dublin), James Walters(Cardiff University), Kai-How Farh(Massachusetts General Hospital), Peter Holmans(Centre for Mental Health), Phil Lee(Broad Institute), Brendan Bulik‐Sullivan(Broad Institute), David Collier(King's College London), Hailiang Huang(Broad Institute), Tune H. Pers(Broad Institute), Ingrid Agartz(University of Oslo), Esben Agerbo(Aarhus University), Margot Albus, Madeline Alexander(Stanford University), Farooq Amin(Emory University), Silviu‐Alin Bacanu(Virginia Commonwealth University), Martin Begemann(Max Planck Institute of Experimental Medicine), Richard A. Belliveau(Broad Institute), Judit Bene(University of Pecs), Sarah E. Bergen(Broad Institute), Elizabeth Bevilacqua(Broad Institute), Tim B. Bigdeli(Virginia Commonwealth University), Donald W. Black(University of Iowa), Richard Bruggeman(University Medical Center Groningen), Nancy G. Buccola(Louisiana State University Health Sciences Center New Orleans), Randy L. Buckner(Harvard University), William Byerley(University of California, San Francisco), Wiepke Cahn(University Medical Center Utrecht), Guiqing Cai(Icahn School of Medicine at Mount Sinai), Dominique Campion(Centre Hospitalier du Rouvray), Rita M. Cantor(University of California, Los Angeles), Vaughan J. Carr(UNSW Sydney), Noa Carrera(Cardiff University), Stanley V. Catts(Royal Brisbane and Women's Hospital), Kimberley D. Chambert(Broad Institute), Raymond C. K. Chan(Institute of Psychology, Chinese Academy of Sciences), Ronald Y. L. Chan(Institute of Psychology, Chinese Academy of Sciences), Eric Chen(University of Hong Kong), Wei Cheng(University of North Carolina at Chapel Hill), Eric F.C. Cheung(Castle Peak Hospital), Siow Ann Chong(Institute of Mental Health), C. Robert Cloninger(Washington University in St. Louis), David Cohen, Nadine Cohen(Janssen (United States)), Paul Cormican(Trinity College Dublin), Nick Craddock(Centre for Mental Health), James J. Crowley(University of North Carolina at Chapel Hill), David Curtis(Queen Mary University of London), Michael Davidson(Sheba Medical Center), Kenneth L. Davis(Icahn School of Medicine at Mount Sinai), Franziska Degenhardt(University of Bonn), Jurgen Del‐Favero(University of Antwerp), Ditte Demontis(Aarhus University), Dimitris Dikeos(National and Kapodistrian University of Athens), Timothy G. Dinan(University College Cork), Srdjan Djurovic(Oslo University Hospital), Gary Donohoe(Ollscoil na Gaillimhe – University of Galway), Elodie Drapeau(Icahn School of Medicine at Mount Sinai), Jubao Duan(NorthShore University HealthSystem), Frank Dudbridge(London School of Hygiene & Tropical Medicine), Naser Durmishi(University Clinic of Traumatology), Peter Eichhammer(University of Regensburg), Johan G. Eriksson(Helsinki University Hospital), Valentina Escott‐Price(Cardiff University), Laurent Essioux(Roche (Switzerland)), Ayman H. Fanous(University of Southern California), Martilias S. Farrell(University of North Carolina at Chapel Hill), Josef Frank(Heidelberg University), Lude Franke(University Medical Center Groningen), Robert Freedman(University of Colorado Denver), Nelson B. Freimer(University of California, Los Angeles), Marion Friedl, Joseph I. Friedman(Icahn School of Medicine at Mount Sinai), Menachem Fromer(Broad Institute), Giulio Genovese(Broad Institute), Lyudmila Georgieva(Cardiff University), Ina Giegling(Ludwig-Maximilians-Universität München), Paola Giusti‐Rodríguez(University of North Carolina at Chapel Hill), Stephanie Godard(Inserm), Jacqueline I. Goldstein(Broad Institute), В. Е. Голимбет(Mental Health Research Center of Russian Academy of Medical Sciences), Srihari Gopal(Janssen (United States)), Jacob Gratten(The University of Queensland), Lieuwe de Haan(University of Amsterdam), Christian Hammer(Max Planck Institute of Experimental Medicine), Marian L. Hamshere(Cardiff University), Mark Hansen(Illumina (United States)), Thomas Folkmann Hansen(Mental Health Services), Vahram Haroutunian(Allen Institute for Brain Science), Annette M. Hartmann, Frans A. Henskens(Schizophrenia Research Institute), Stefan Herms(University of Bonn), Joel N. Hirschhorn(Broad Institute), Per Hoffmann(University of Bonn), Andrea Hofman(University of Bonn), Mads V. Hollegaard(Statens Serum Institut), David M. Hougaard(Statens Serum Institut), Masashi Ikeda(Fujita Health University), Inge Joa(Stavanger University Hospital), Antonio Julià(Vall d'Hebron Institut de Recerca), Luba Kalaydjieva(The University of Western Australia), Sena Karachanak-Yankova(Medical University of Sofia), Juha Karjalainen(University Medical Center Groningen), David Kavanagh(Cardiff University), Matthew C. Keller(University of Colorado Boulder), James L. Kennedy(Centre for Addiction and Mental Health), Andrey Khrunin(Institute of Molecular Genetics), Yunjung Kim(University of North Carolina at Chapel Hill), Jānis Kloviņš(Latvian Biomedical Research and Study Centre), James A. Knowles(University of Southern California), Bettina Konte, Vaidutis Kučinskas(Vilnius University), Zita Aušrelė Kučinskienė(Vilnius University), Hana Kuzelova-Ptackova(Charles University), Anna K. Kähler(Karolinska Institutet), Claudine Laurent(Sorbonne Université), Jimmy Lee(Duke-NUS Medical School), Sang Lee(The University of Queensland), Sophie E. Legge(Cardiff University), Bernard Lerer(Hadassah Medical Center), Miaoxin Li(University of Hong Kong), Tao Li(Sichuan University), Kung‐Yee Liang(Johns Hopkins University), Jeffrey A. Lieberman(Columbia University), Limborskaia Sa(Institute of Molecular Genetics), Carmel M. Loughland(Schizophrenia Research Institute), Jan Lubiński(International Hereditary Cancer Center), Jouko Lönnqvist(Finnish Institute for Health and Welfare), Milan Maçek(Charles University), Patrik K. E. Magnusson(Karolinska Institutet), Brion S. Maher(Johns Hopkins University), Wolfgang Maier(University of Bonn), Jacques Mallet(Centre National de la Recherche Scientifique), Sara Marsal(Vall d'Hebron Institut de Recerca), Manuel Mattheisen(University of Bonn), Morten Mattingsdal(University of Oslo), Robert W. McCarley(Harvard University), Colm McDonald(Ollscoil na Gaillimhe – University of Galway), Andrew M. McIntosh(University of Edinburgh), Sandra Meier(Heidelberg University), Carin J. Meijer(University of Amsterdam), Béla Melegh(University of Pecs), Ingrid Melle(Oslo University Hospital), Raquelle I. Mesholam‐Gately(Beth Israel Deaconess Medical Center), Andres Metspalu(University of Tartu), Patricia T. Michie(Schizophrenia Research Institute), Lili Milani(University of Tartu), Vihra Milanova(Medical University of Sofia), Younes Mokrab(Eli Lilly (United Kingdom)), Derek W. Morris(Ollscoil na Gaillimhe – University of Galway), Ole Mors(Aarhus University), Kieran C. Murphy(Royal College of Surgeons in Ireland), Robin Murray(King's College London), Inez Myin‐Germeys(Maastricht University Medical Centre), Bertram Müller‐Myhsok(University of Liverpool), Mari Nelis(University of Tartu), Igor Nenadić(Jena University Hospital), Deborah A. Nertney(The University of Queensland), Gerald Nestadt(Johns Hopkins University), Kristin K. Nicodemus(Trinity College Dublin), Liene Ņikitina-Zaķe(Latvian Biomedical Research and Study Centre), Laura Nisenbaum(Eli Lilly (United States)), Annelie Nordin(Umeå University), Eadbhard O’Callaghan, Colm O’Dushlaine(Broad Institute), F. Anthony O’Neill(Queen's University Belfast), Sang-Yun Oh(Lawrence Berkeley National Laboratory), Ann Olincy(University of Colorado Denver), Line Olsen(Mental Health Services), Jim van Os(King's College London), Christos Pantelis(The University of Melbourne), George N. Papadimitriou(National and Kapodistrian University of Athens), Sergi Papiol(Max Planck Institute of Experimental Medicine), Elena Parkhomenko(Icahn School of Medicine at Mount Sinai), Michele T. Pato(University of Southern California), Tiina Paunio(University of Helsinki), Milica Pejović-Milovančević(University of Belgrade), Diana O. Perkins(University of North Carolina at Chapel Hill), Olli Pietiläinen(Institute for Molecular Medicine Finland), Jonathan Pimm(University College London), Andrew Pocklington(Cardiff University), Alkes L. Price(Harvard University), Ann E. Pulver(Johns Hopkins University), Shaun Purcell(Icahn School of Medicine at Mount Sinai), Digby Quested(University of Oxford), Henrik Berg Rasmussen(Mental Health Services), Abraham Reichenberg(Icahn School of Medicine at Mount Sinai), Mark A. Reimers(Virginia Commonwealth University), Alexander Richards(Centre for Mental Health), Joshua L. Roffman(Massachusetts General Hospital), Panos Roussos(Icahn School of Medicine at Mount Sinai), Douglas M. Ruderfer(Icahn School of Medicine at Mount Sinai), Veikko Salomaa(Finnish Institute for Health and Welfare), Alan R. Sanders(NorthShore University HealthSystem), Ulrich Schall(Schizophrenia Research Institute), Christian Schubert(Pfizer (United States)), Thomas G. Schulze(Heidelberg University), Sibylle G. Schwab, Edward M. Scolnick(Broad Institute), Rodney J. Scott(Hunter New England Local Health District), Larry J. Seidman(Beth Israel Deaconess Medical Center), Jianxin Shi(National Cancer Institute), Engilbert Sigurðsson(University of Iceland), Teimuraz Silagadze(Tbilisi State Medical University), Jeremy M. Silverman(Veterans Health Administration), Kang Sim(Institute of Mental Health), P. A. Slominsky(Institute of Molecular Genetics), Jordan W. Smoller(Broad Institute), Hon‐Cheong So(University of Hong Kong), Chris C. A. Spencer(Centre for Human Genetics), Eli A. Stahl(Broad Institute), Hreinn Stefánsson(deCODE Genetics (Iceland)), Stacy Steinberg(deCODE Genetics (Iceland)), Elisabeth Stögmann(Medical University of Vienna), Richard E. Straub(Lieber Institute for Brain Development), Eric Strengman(University Medical Center Utrecht), Jana Strohmaier(Heidelberg University), T. Scott Stroup(Columbia University), Mythily Subramaniam(Institute of Mental Health), Jaana Suvisaari(Finnish Institute for Health and Welfare), Dragan M. Švrakić(Washington University in St. Louis), Jin P. Szatkiewicz(University of North Carolina at Chapel Hill), Erik Söderman(Karolinska Institutet), Srinivas Thirumalai(Berkshire Healthcare NHS Foundation Trust), Драга Тончева(Medical University of Sofia), Sarah Tosato(University of Verona), Juha Veijola(Oulu University Hospital), John L. Waddington(Royal College of Surgeons in Ireland), Dermot Walsh(Health Research Board), Dai Wang(Janssen (United States)), Qiang Wang(Sichuan University), Bradley T. Webb(Virginia Commonwealth University), Mark Weiser(Sheba Medical Center), Dieter B. Wildenauer(Queen Elizabeth II Medical Centre), Nigel Williams(Cardiff University), Stephanie Williams(University of North Carolina at Chapel Hill), Stephanie H. Witt(Heidelberg University), Aaron R. Wolen(Virginia Commonwealth University), Emily Wong(University of Hong Kong), Brandon K. Wormley(Virginia Commonwealth University), Hualin Simon Xi(Pfizer (United States)), Clement C. Zai(Centre for Addiction and Mental Health), Xuebin Zheng(Genome Institute of Singapore), Fritz Zimprich(Medical University of Vienna), Naomi R. Wray(The University of Queensland), Kāri Stefánsson(deCODE Genetics (Iceland)), Peter M. Visscher(The University of Queensland), Rolf Adolfsson(Umeå University), Ole A. Andreassen(Oslo University Hospital), Douglas Blackwood(University of Edinburgh), Elvira Bramon(University College London), Joseph D. Buxbaum(Allen Institute for Brain Science), Anders D. Børglum(Aarhus University), Ariel Darvasi(Hebrew University of Jerusalem), Enrico Domenici(Roche (Switzerland)), Hannelore Ehrenreich(Max Planck Institute of Experimental Medicine), Tõnu Esko(Broad Institute), Pablo V. Gejman(NorthShore University HealthSystem), Michael Gill(Trinity College Dublin), Hugh Gurling(University College London), Christina M. Hultman(Karolinska Institutet), Nakao Iwata(Fujita Health University), Assen Jablensky(The University of Western Australia), Erik G. Jönsson(Karolinska Institutet), Kenneth S. Kendler(Virginia Commonwealth University), George Kirov(Cardiff University), Jo Knight(Centre for Addiction and Mental Health), Todd Lencz(Feinstein Institute for Medical Research), Douglas F. Levinson(Stanford University), Qingqin S. Li(Janssen (United States)), Jianjun Liu(National University of Singapore), Anil K. Malhotra(Feinstein Institute for Medical Research), Steven A. McCarroll(Broad Institute), Andrew McQuillin(University College London), Jennifer L. Moran(Broad Institute), Preben Bo Mortensen(Aarhus University), Bryan Mowry(The University of Queensland), Michael J. Owen(Centre for Mental Health), Aarno Palotie(Broad Institute), Carlos N. Pato(University of Southern California), Tracey L. Petryshen(Broad Institute), Daniëlle Posthuma(Amsterdam Neuroscience), Brien P. Riley(Virginia Commonwealth University), Dan Rujescu(Ludwig-Maximilians-Universität München), Pak C. Sham(University of Hong Kong), Pamela Sklar(Allen Institute for Brain Science), David St Clair(University of Aberdeen), Daniel R. Weinberger(Johns Hopkins University), Jens R. Wendland(Pfizer (United States)), Thomas Werge(University of Copenhagen), Mark J. Daly(Massachusetts General Hospital), Patrick F. Sullivan(University of North Carolina at Chapel Hill), Michael O‘Donovan(Centre for Mental Health)
Cited by 155Open Access
Abstract
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.
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