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Record W2734344008 · doi:10.1101/143933

The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

2017· preprint· en· W2734344008 on OpenAlexaff
NA Patsopoulos, Sergio E. Baranzini, Adam Santaniello, Parisa Shoostari, Chris Cotsapas, G Wong, AH Beecham, Tojo James, Jeri Replogle, Ioannis S. Vlachos, Cristin McCabe, Tune H. Pers, Aaron Brandes, Charles C. White, Brendan T Keenan, Maria Cimpean, Philip Winn, IP Panteliadis, A K Robbins, Onigiusz Zarzycki, Bénédicte Dubois, An Goris, Helle Bach Søndergaard, Finn Sellebjerg, Per Soelberg Sorensen, Henrik Ullum, Lise Wegner Thoerner, Janna Saarela, I. Rebeix, Vincent Damotte, Bertrand Fontaine, Léna Guillot Noel, Mark Lathrop, Sandra Vukusik, Achim Berthele, Viola Biberacher, Dorothea Buck, Christiane Gasperi, Christiane Graetz, Verena Grummel, Bernhard Hemmer, Muna Hoshi, Benjamin Knier, Thomas Korn, CM Lill, Felix Luessi, Mark Mühlau, Frauke Zipp, Efthimios Dardiotis, Cristina Agliardi, Antonio Amoroso, Nadia Barizzone, Maria Donata Benedetti, Luisa Bernardinelli, Paola Cavalla, Ferdinando Clarelli, Giacomo P. Comi, Daniele Cusi, Federica Esposito, Laura Ferrè, Daniela Galimberti, Clara Guaschino, MA Leone, V. Martinelli, Lucia Moiola, Marco Salvetti, Melissa Sorosina, Domizia Vecchio, Andrea Zauli, Silvia Santoro, Miriam Zuccalà, Julia Mescheriakova, Cornelia M. van Duijn, S.D. Bos, EG Celius, Anne Spurkland, Manuel Comabella, Xavier Montalbán, Lars Alfredsson, Izaura Lima Bomfim, David Gómez-Cabrero, Jan Hillert, Maja Jagodic, Magdalena Lindén, Fredrik Piehl, Ilijas Jelčić, Roland Martinꝉ, Mireia Sospedra, Amie Baker, Maria Ban, Clive Hawkins, Pirro G. Hysi, Seema Kalra, Fredrik Karpe, Jyoti Khadake, Geneviève Lachance, Paul Molyneux, Matt J. Neville, John Thorpe, Elizabeth M. Bradshaw, SJ Caillier, Peter A. Calabresi, BAC Cree, Anne H. Cross, Michael Davis, PWI de Bakker, Silvia Delgado, M Dembélé, David Edwards, Kathryn C. Fitzgerald, I. Fröhlich, Pierre‐Antoine Gourraud, Haines Jl, Håkon Håkonarson, Dorlan Kimbrough, Noriko Isobe, Ioanna Konidari, Ellen Lathi, MH Lee, T Li, An Ding, Andrew Zimmer, Acy Lo, Lohith Madireddy, CP Manrique, Mitja Mitrovič, Marta Olah, Ellis Patrick, MA Pericak-Vance, Laura Piccio, Catherine Schaefer, Howard L. Weiner, Kasper Lage, Alastair Compston, David A. Hafler, HF Harbo, SL Hauser, Graeme J. Stewart, Sandra D’Alfonso, Georgios M. Hadjigeorgiou, Bruce Taylor, L F Barcellos, David R. Booth, Rogier Hintzen, Ingrid Kockum, Filippo Martinelli Boneschi, Jacob L. McCauley, J. Oksenberg, Annette Oturai, Stephen Sawcer, AJ Ivinson, Tomas Olsson, PL De Jager, Murray L. Barclay, Laurent Peyrin‐Biroulet, Mathias Chamaillard, Jean-Frederick Colombe, Mario Cottone, Anthony Croft, R. D’Incà, Jonas Halfvarson, Katherine Hanigan, Paul Henderson, Jean‐Pierre Hugot, Amir Karban, Nicholas A. Kennedy, Mohammed Azam Khan, Marc Lémann, Arie Levine, Dunecan Massey, Mónica Milla, Grant W. Montgomery, Sok Meng Evelyn Ng, Ioannis Oikonomou, Harald Peeters, Deborah D. Proctor, Jean‐François Rahier, Rebecca Roberts, Paul Rutgeerts, Frank Seibold, Laura Stronati, Kirstin M. Taylor, Leif Törkvist, Kullak Ublick, Johan Van Limbergen, A. Van Gossum, Morten H. Vatn, Hu Zhang, Wei Zhang

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2017
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsMcGill University and Génome Québec Innovation Centre
FundersNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeNational Institutes of HealthH. Lundbeck A/SNational Multiple Sclerosis SocietyVlaamse regeringNorges ForskningsrådVetenskapsrådetKnut och Alice Wallenbergs StiftelseKU LeuvenFonds Wetenschappelijk OnderzoekAFA FörsäkringLundbeckfondenInstitut National de la Santé et de la Recherche MédicaleMedical Research CouncilStrategiske ForskningsrådEuropean CommissionFondation pour l'Aide à la Recherche sur la Sclérose en PlaquesKing's College LondonBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchMultiple Sclerosis SocietyNational Institute of Allergy and Infectious DiseasesAgence Nationale de la RechercheWellcome TrustBiogenHarvard NeuroDiscovery CenterForskningsrådet om Hälsa, Arbetsliv och VälfärdScleroseforeningen
KeywordsMultiple sclerosisMicrogliaImmune systemMajor histocompatibility complexBiologyGeneImmunologyInnate immune systemGeneticsNeuroscienceInflammation

Abstract

fetched live from OpenAlex

Abstract: We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system. One Sentence Summary: We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.

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 imitation

Not 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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.194
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.013
GPT teacher head0.199
Teacher spread0.186 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
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

Citations116
Published2017
Admission routes1
Has abstractyes

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