Genetic correlation between amyotrophic lateral sclerosis and schizophrenia
Authors: McLaughlin Russell L. , Schijven Dick , van Rheenen Wouter , van Eijk Kristel R. , O’Brien Margaret , Kahn René S. , Ophoff Roel A. , Goris An , Bradley Daniel G. , Al-Chalabi Ammar , van den Berg Leonard H. , Luykx Jurjen J. , Hardiman Orla , Veldink Jan H. ,   Project MinE GWAS Consortium, Shatunov Aleksey , Dekker Annelot M. , Diekstra Frank P. , Pulit Sara L. , van der Spek Rick A. A. , van Doormaal Perry T. C. , Sproviero William , Jones Ashley R. , Nicholson Garth A. , Rowe Dominic B. , Pamphlett Roger , Kiernan Matthew C. , Bauer Denis , Kahlke Tim , Williams Kelly , Eftimov Filip , Fogh Isabella , Ticozzi Nicola , Lin Kuang , Millecamps Stéphanie , Salachas François , Meininger Vincent , de Carvalho Mamede , Pinto Susana , Mora Jesus S. , Rojas-García Ricardo , Polak Meraida , Chandran Siddharthan , Colville Shuna , Swingler Robert , Morrison Karen E. , Shaw Pamela J. , Hardy John , Orrell Richard W. , Pittman Alan , Sidle Katie , Fratta Pietro , Malaspina Andrea , Petri Susanne , Abdulla Susanna , Drepper Carsten , Sendtner Michael , Meyer Thomas , Wiedau-Pazos Martina , Lomen-Hoerth Catherine , Van Deerlin Vivianna M. , Trojanowski John Q. , Elman Lauren , McCluskey Leo , Basak Nazli , Meitinger Thomas , Lichtner Peter , Blagojevic-Radivojkov Milena , Andres Christian R. , Maurel Cindy , Bensimon Gilbert , Landwehrmeyer Bernhard , Brice Alexis , Payan Christine A. M. , Saker-Delye Safa , Dürr Alexandra , Wood Nicholas , Tittmann Lukas , Lieb Wolfgang , Franke Andre , Rietschel Marcella , Cichon Sven , Nöuthen Markus M. , Amouyel Philippe , Tzourio Christophe , Dartigues Jean- François , Uitterlinden Andre G. , Rivadeneira Fernando , Estrada Karol , Hofman Albert , Curtis Charles , van der Kooi Anneke J. , de Visser Marianne , Weber Markus , Shaw Christopher E. , Smith Bradley N. , Pansarasa Orietta , Cereda Cristina , Del Bo Roberto , Comi Giacomo P. , D’Alfonso Sandra , Bertolin Cinzia , Sorarù Gianni , Mazzini Letizia , Pensato Viviana , Gellera Cinzia , Tiloca Cinzia , Ratti Antonia , Calvo Andrea , Moglia Cristina , Brunetti Maura , Arcuti Simon , Capozzo Rosa , Zecca Chiara , Lunetta Christian , Penco Silvana , Riva Nilo , Padovani Alessandro , Filosto Massimiliano , Blair Ian , Leigh P Nigel , Casale Federico , Chio Adriano , Beghi Ettore , Pupillo Elisabetta , Tortelli Rosanna , Logroscino Giancarlo , Powell John , Ludolph Albert C. , Weishaupt Jochen H. , Robberecht Wim , Van Damme Philip , Brown Robert H. , Glass Jonathan , Landers John E. , Andersen Peter M. , Corcia Philippe , Vourc'h Patrick , Silani Vincenzo , van Es Michael A. , Pasterkamp R Jeroen , Lewis Cathryn M. , Breen Gerome ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ripke Stephan , Neale Benjamin M. , Corvin Aiden , Walters James T. R. , Farh Kai-How , Holmans Peter A , Lee Phil , Bulik-Sullivan Brendan , Collier David A. , Huang Hailiang , Pers Tune H. , Agartz Ingrid , Agerbo Esben , Albus Margot , Alexander Madeline , Amin Farooq , Bacanu Silviu A. , Begemann Martin , Belliveau Richard A. , Bene Judit , Bergen Sarah E. , Bevilacqua Elizabeth , Bigdeli Tim B. , Black Donald W. , Bruggeman Richard , Buccola Nancy G. , Buckner Randy L. , Byerley William , Cahn Wiepke , Cai Guiqing , Campion Dominique , Cantor Rita M. , Carr Vaughan J. , Carrera Noa , Catts Stanley V. , Chambert Kimberley D. , Chan Raymond C. K. , Chan Ronald Y. L. , Chen Eric Y. H. , Cheng Wei , Cheung Eric F. C. , Chong Siow Ann , Cloninger C Robert , Cohen David , Cohen Nadine , Cormican Paul , Craddock Nick , Crowley James J. , Curtis David , Davidson Michael , Davis Kenneth L. , Degenhardt Franziska , Del Favero Jurgen , Demontis Ditte , Dikeos Dimitris , Dinan Timothy , Djurovic Srdjan , Donohoe Gary , Drapeau Elodie , Duan Jubao , Dudbridge Frank , Durmishi Naser , Eichhammer Peter , Eriksson Johan , Escott-Price Valentina , Essioux Laurent , Fanous Ayman H. , Farrell Martilias S. , Frank Josef , Franke Lude , Freedman Robert , Freimer Nelson B. , Friedl Marion , Friedman Joseph I. , Fromer Menachem , Genovese Giulio , Georgieva Lyudmila , Giegling Ina , Giusti-Rodríguez Paola , Godard Stephanie , Goldstein Jacqueline I. , Golimbet Vera , Gopal Srihari , Gratten Jacob , de Haan Lieuwe , Hammer Christian , Hamshere Marian L. , Hansen Mark , Hansen Thomas , Haroutunian Vahram , Hartmann Annette M. , Henskens Frans A. , Herms Stefan , Hirschhorn Joel N. , Hoffmann Per , Hofman Andrea , Hollegaard Mads V. , Hougaard David M. , Ikeda Masashi , Joa Inge , Julià Antonio , Kalaydjieva Luba , Karachanak-Yankova Sena , Karjalainen Juha , Kavanagh David , Keller Matthew C. , Kennedy James L. , Khrunin Andrey , Kim Yunjung , Klovins Janis , Knowles James A. , Konte Bettina , Kucinskas Vaidutis , Kucinskiene Zita Ausrele , Kuzelova-Ptackova Hana , Kähler Anna K. , Laurent Claudine , Lee Jimmy , Lee S Hong , Legge Sophie E. , Lerer Bernard , Li Miaoxin , Li Tao , Liang Kung-Yee , Lieberman Jeffrey , Limborska Svetlana , Loughland Carmel M. , Lubinski Jan , Lönnqvist Jouko , Macek Milan , Magnusson Patrik K. E. , Maher Brion S. , Maier Wolfgang , Mallet Jacques , Marsal Sara , Mattheisen Manuel , Mattingsdal Morten , McCarley Robert W. , McDonald Colm , McIntosh Andrew M. , Meier Sandra , Meijer Carin J. , Melegh Bela , Melle Ingrid , Mesholam-Gately Raquelle I. , Metspalu Andres , Michie Patricia T. , Milani Lili , Milanova Vihra , Mokrab Younes , Morris Derek W. , Mors Ole , Murphy Kieran C. , Murray Robin M. , Myin-Germeys Inez , Müller-Myhsok Bertram , Nelis Mari , Nenadic Igor , Nertney Deborah A. , Nestadt Gerald , Nicodemus Kristin K. , Nikitina-Zake Liene , Nisenbaum Laura , Nordin Annelie , O’Callaghan Eadbhard , O’Dushlaine Colm , O’Neill F Anthony , Oh Sang-Yun , Olincy Ann , Olsen Line , Van Os Jim , Pantelis Christos , Papadimitriou George N. , Papiol Sergi , Parkhomenko Elena , Pato Michele T. , Paunio Tiina , Pejovic-Milovancevic Milica , Perkins Diana O. , Pietiläinen Olli , Pimm Jonathan , Pocklington Andrew J. , Price Alkes , Pulver Ann E. , Purcell Shaun M. , Quested Digby , Rasmussen Henrik B. , Reichenberg Abraham , Reimers Mark A. , Richards Alexander L. , Roffman Joshua L. , Roussos Panos , Ruderfer Douglas M. , Salomaa Veikko , Sanders Alan R. , Schall Ulrich , Schubert Christian R. , Schulze Thomas G. , Schwab Sibylle G. , Scolnick Edward M. , Scott Rodney J. , Seidman Larry J. , Shi Jianxin , Sigurdsson Engilbert , Silagadze Teimuraz , Silverman Jeremy M. , Sim Kang , Slominsky Petr , Smoller Jordan W. , So Hon-Cheong , Spencer Chris C. A. , Stahl Eli A. , Stefansson Hreinn , Steinberg Stacy , Stogmann Elisabeth , Straub Richard E. , Strengman Eric , Strohmaier Jana , Stroup T Scott , Subramaniam Mythily , Suvisaari Jaana , Svrakic Dragan M. , Szatkiewicz Jin P. , Söderman Erik , Thirumalai Srinivas , Toncheva Draga , Tosato Sarah , Veijola Juha , Waddington John , Walsh Dermot , Wang Dai , Wang Qiang , Webb Bradley T. , Weiser Mark , Wildenauer Dieter B. , Williams Nigel M. , Williams Stephanie , Witt Stephanie H. , Wolen Aaron R. , Wong Emily H. M. , Wormley Brandon K. , Xi Hualin Simon , Zai Clement C. , Zheng Xuebin , Zimprich Fritz , Wray Naomi R. , Stefansson Kari , Visscher Peter M. , Adolfsson Rolf , Andreassen Ole A. , Blackwood Douglas H. R. , Bramon Elvira , Buxbaum Joseph D. , Børglum Anders D. , Darvasi Ariel , Domenici Enrico , Ehrenreich Hannelore , Esko Tõnu , Gejman Pablo V. , Gill Michael , Gurling Hugh , Hultman Christina M. , Iwata Nakao , Jablensky Assen V. , Jönsson Erik G. , Kendler Kenneth S. , Kirov George , Knight Jo , Lencz Todd , Levinson Douglas F. , Li Qingqin S. , Liu Jianjun , Malhotra Anil K. , McCarroll Steven A. , McQuillin Andrew , Moran Jennifer L. , Mortensen Preben B. , Mowry Bryan J. , Owen Michael J. , Palotie Aarno , Pato Carlos N. , Petryshen Tracey L. , Posthuma Danielle , Riley Brien P. , Rujescu Dan , Sham Pak C. , Sklar Pamela , St Clair David , Weinberger Daniel R. , Wendland Jens R. , Werge Thomas , Daly Mark J. , Sullivan Patrick F. , O’Donovan Michael C. 
Published: March 2017

AbstractWe 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.