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Genetic correlation between amyotrophic lateral sclerosis and schizophrenia
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, Aleksey Shatunov, Annelot M. Dekker, Frank P. Diekstra, Sara L. Pulit, Rick A. A. van der Spek, Perry T.C. van Doormaal, William Sproviero, Garth A. Nicholson, Dominic B. Rowe, Roger Pamphlett, Matthew C. Kiernan, Denis C. Bauer, Tim Kahlke, Kelly L. Williams, Filip Eftimov, Isabella Fogh, Nicola Ticozzi, Kuang Lin, Stéphanie Millecamps, François Salachas, Vincent Meininger, Mamede de Carvalho, Susana Pinto, Jesús S. Mora, Ricardo Rojas-García, Meraida Polak, Siddharthan Chandran, Shuna Colville, Robert Swingler, Karen 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, Nazlı Başak, Thomas Meitinger, Peter Lichtner, Milena Blagojevic-Radivojkov, Christian Andrés, Cindy Maurel, Gilbert Bensimon, G. Bernhard Landwehrmeyer, Alexis Brice, Christine Payan, Safa Saker-Delye, Alexandra Dürr, Nicholas Wood, Lukas Tittmann, Wolfgang Lieb, André Franke, Marcella Rietschel, Sven Cichon, Markus M. Nöuthen, Philippe Amouyel, Christophe Tzourio, Jean François Dartigues, André G. Uitterlinden, Fernando Rivadeneira, Karol Estrada, Albert Hofman, Charles Curtis, Anneke J. van der Kooi, Marianne de Visser, Markus Weber, Christopher E. Shaw, Bradley Smith, Orietta Pansarasa, Cristina Cereda, Roberto Del Bo, Giacomo P. Comi, Sandra D’Alfonso, Cinzia Bertolin, Gianni Sorarú, 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 P. Blair, P. Nigel Leigh, Federico Casale, Adriano Chiò, 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 D. 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, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James Walters, Kai-How Farh, Peter Holmans, Phil Lee, Brendan Bulik‐Sullivan, David Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu‐Alin 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 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 G. Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan G. 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, В. Е. Голимбет, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Thomas Folkmann 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, Jānis Kloviņš, James A. Knowles, Bettina Konte, Vaidutis Kučinskas, Zita Aušrelė Kučinskienė, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, Sang Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung‐Yee Liang, Jeffrey A. Lieberman, Limborskaia Sa, Carmel M. Loughland, Jan Lubiński, Jouko Lönnqvist, Milan Maçek, 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, Béla 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 Murray, Inez Myin‐Germeys, Bertram Müller‐Myhsok, Mari Nelis, Igor Nenadić, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Ņikitina-Zaķe, 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 Pejović-Milovančević, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew Pocklington, Alkes L. Price, Ann E. Pulver, Shaun Purcell, Digby Quested, Henrik Berg Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurðsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, P. A. Slominsky, Jordan W. Smoller, Hon‐Cheong So, Chris C. A. Spencer, Eli A. Stahl, Hreinn Stefánsson, Stacy Steinberg, Elisabeth Stögmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Švrakić, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Драга Тончева, Sarah Tosato, Juha Veijola, John L. Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kāri Stefánsson, Peter M. Visscher, Rolf Adolfsson, Ole A. Andreassen, Douglas 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 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 Bo Mortensen, Bryan Mowry, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Daniëlle 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 O‘Donovan
Bibliographic record
VenueNature Communications · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersNational Institute of Neurological Disorders and StrokeNational Heart, Lung, and Blood InstituteEconomic and Social Research CouncilMedical Research CouncilCentre hospitalier régional universitaire de LilleNational Institute of Mental HealthKU LeuvenMinistero dell’Istruzione, dell’Università e della RicercaErasmus Medisch CentrumZonMwNational Institutes of HealthRosetrees TrustKing's College LondonHjartaverndDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseE-RareScience Foundation IrelandNational Institute on AgingNational Institute for Health and Care ResearchHealth Research BoardBundesministerium für Bildung und ForschungLundbeckfondenInstitut National de la Santé et de la Recherche MédicaleEU Joint Programme – Neurodegenerative Disease ResearchParkinson's UKMotor Neurone Disease AssociationSouth London and Maudsley NHS Foundation TrustAgence Nationale de la RechercheWellcome TrustALS AssociationAlzheimer's Association
KeywordsAmyotrophic lateral sclerosisSchizophrenia (object-oriented programming)CorrelationMedicineGeneticsBiologyNeurosciencePsychiatryDiseasePathologyMathematics
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.014
Threshold uncertainty score0.677
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.027
GPT teacher head0.296
Teacher spread0.269 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations156
Published2017
Admission routes1
Has abstractyes