Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

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Author(s)
Patsopoulos, Nikolas A
Baranzini, Sergio E
Santaniello, Adams
Shoostari, Parisa
Cotsapas, Chris
Wong, Garrett
Beecham, Ashley H
James, Tojo
Replogle, Joseph
Vlachos, Ioannis S
McCabe, Cristin
Pers, Tune H
Brandes, Aaron
White, Charles
Keenan, Brendan
Cimpean, Maria
Winn, Phoebe
Panteliadis, Ioannis-Pavlos
Robbins, Allison
Andlauer, Till FM
Zarzycki, Onigiusz
Dubois, Benedicte
Goris, An
Sondergaard, Helle Bach
Sellebjerg, Finn
Sorensen, Per Soelberg
Ullum, Henrik
Thorner, Lise Wegner
Saarela, Janna
Cournu-Rebeix, Isabelle
Damotte, Vincent
Fontaine, Bertrand
Guillot-Noel, Lena
Lathrop, Mark
Vukusic, Sandra
Berthele, Achim
Pongratz, Viola
Pongratz, Viola
Gasperi, Christiane
Graetz, Christiane
Grummel, Verena
Hemmer, Bernhard
Hoshi, Muni
Knier, Benjamin
Korn, Thomas
Lill, Christina M
Luessi, Felix
Muehlau, Mark
Zipp, Frauke
Dardiotis, Efthimios
Agliardi, Cristina
Amoroso, Antonio
Barizzone, Nadia
Benedetti, Maria D
Bernardinelli, Luisa
Cavalla, Paola
Clarelli, Ferdinando
Comi, Giancarlo
Cusi, Daniele
Esposito, Federica
Ferre, Laura
Galimberti, Daniela
Guaschino, Clara
Leone, Maurizio A
Martinelli, Vittorio
Moiola, Lucia
Salvetti, Marco
Sorosina, Melissa
Vecchio, Domizia
Zauli, Andrea
Santoro, Silvia
Mancini, Nicasio
Zuccala, Miriam
Mescheriakova, Julia
van Duijn, Cornelia
Bos, Steffan D
Celius, Elisabeth G
Spurkland, Anne
Comabella, Manuel
Montalban, Xavier
Alfredsson, Lars
Bomfim, Izaura L
Gomez-Cabrero, David
Hillert, Jan
Jagodic, Maja
Linden, Magdalena
Piehl, Fredrik
Jelcic, Ilijas
Martin, Roland
Sospedra, Mirela
Baker, Amie
Ban, Maria
Hawkins, Clive
Hysi, Pirro
Kalra, Seema
Karpe, Fredrik
Khadake, Jyoti
Lachance, Genevieve
Molyneux, Paul
Neville, Matthew
Thorpe, John
Bradshaw, Elizabeth
Caillier, Stacy J
Calabresi, Peter
Cree, Bruce AC
Cross, Anne
Davis, Mary
de Bakker, Paul WI
Delgado, Silvia
Dembele, Marieme
Edwards, Keith
Fitzgerald, Kate
Frohlich, Irene Y
Gourraud, Pierre-Antoine
Haines, Jonathan L
Hakonarson, Hakon
Kimbrough, Dorlan
Isobe, Noriko
Konidari, Ioanna
Lathi, Ellen
Lee, Michelle H
Li, Taibo
An, David
Zimmer, Andrew
Madireddy, Lohith
Manrique, Clara P
Mitrovic, Mitja
Olah, Marta
Patrick, Ellis
Pericak-Vance, Margaret A
Piccio, Laura
Schaefer, Cathy
Weiner, Howard
Lage, Kasper
Scott, Rodney J
Lechner-Scott, Jeannette
Leal, Rod
Moscato, Pablo
Booth, David R
Stewart, Graeme J
Vucic, Stephen
Pame, Grant
BamettO, Michael
Mason, Deborah
GriffithS, Lyn
Broadley, Simon
Tajouri, Lotti
Baxter, Alan
Slee, Mark
Taylor, Bruce V
Charlesworth, Jac
Kilpatrick, Trevor J
Rubio, Justin
Jokubaitis, Vilija
Wiley, James
Butzkueven, Helmut
Leslie, Stephen
Motyer, Allan
Stankovich, Jim
Carroll, William M
Kermode, Allan G
Edrin, Marzena
Barclay, Murray
Peyrin-Biroulet, Laurent
Chamaillard, Mathias
Colombe, Jean-Frederick
Cottone, Mario
Croft, Anthony
D'Inca, Renata
Halfvarson, Jonas
Hanigan, Katherine
Henderson, Paul
Hugot, Jean-Pierre
Karban, Amir
Kennedy, Nicholas A
Khan, Mohammed Azam
Lemann, Marc
Levine, Arie
Massey, Dunecan
Milla, Monica
Motoey, Grant W
Ng, Sok Meng Evelyn
Oikonomnou, Joannis
Peeters, Harald
Proctor, Deborah D
Rahier, Jean-Francois
Roberts, Rebecca
Rutgeerts, Paul
Seibold, Frank
Stronati, Laura
Taylor, Kirstin M
Torkvist, Leif
Ublick, Kullak
Van Limbergen, Johan
Van Gossum, Andre
Vatn, Morten H
Zhang, Hu
Zhang, Wei
Donnelly, Peter
Barroso, Ines
Blackwe, Jenefer M
Bramon, Elvira
Brown, Matthew A
Casas, Juan P
Corvin, Aiden
Deloukas, Panos
Duncanson, Audrey
Jankowski, Janusz
Markus, Hugh S
Mathew, Christopher G
Palmer, Colin NA
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J
Trembath, Richard C
Viswanathan, Ananth C
Wood, Nicholas W
Spencer, Chris CA
Band, Gavin
Bellenguez, Celine
Freeman, Colin
Hellenthal, Garrett
Giannoulatou, Eleni
Pirinen, Matti
Pearson, Richard
Strange, Amy
Sul, Zhan
Vukcevic, Damj An
Donnelly, Peter
Langford, Cordelia
Hunt, Sarah E
Edkins, Sarah
Gwilliam, Rhian
Blackburn, Hannah
Bumpstead, Suzannah J
Dronov, Serge
Gillman, Matthew
Gray, Emma
Hammond, Naomi
Jayakumar, Alagurevathi
McCann, Owen T
Liddle, Jennifer
Potter, Simon C
Ravindrarajah, Radhi
Ricketts, Michelle
Waller, Matthew
Weston, Paul
Widaa, Sara
Whittaker, Pamela
Barroso, Ines
Deloukas, Panos
Mathew, Christopher G
Blackwe, Jenefer M
Brown, Matthew A
Corvin, Aiden
Spencer, Chris CA
Compston, Alastair
Hafler, David
Harbo, Hanne F
Hauser, Stephen L
Stewart, Graeme
D'Alfonso, Sandra
Hadjigeorgiou, Georgios
Taylor, Bruce
Barcellos, Lisa F
Booth, David
Hintzen, Rogier
Kockum, Ingrid
Martinelli-Boneschi, Filippo
McCauley, Jacob L
Oksenberg, Jorge R
Oturai, Annette
Sawcer, Stephen
Ivinson, Adrian J
Olsson, Tomas
De Jager, Philip L
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2019
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Abstract

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established 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 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative 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 observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

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Science

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365

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6460

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© The Author(s) 2019. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 2019, 365 (6460), pp. 1417-+, DOI: http://doi.org/10.1126/science.aav7188.

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Clinical sciences

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Multidisciplinary Sciences

Science & Technology - Other Topics

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Patsopoulos, NA; Baranzini, SE; Santaniello, A; Shoostari, P; Cotsapas, C; Wong, G; Beecham, AH; James, T; Replogle, J; Vlachos, IS; McCabe, C; Pers, TH; Brandes, A; Broadley, S; et al., Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility, Science, 2019, 365 (6460)

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