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

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    Broadley263156-Accepted.pdf (1.026Mb)
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    Accepted Manuscript (AM)
    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
    Griffith University Author(s)
    Broadley, Simon
    Year published
    2019
    Metadata
    Show full item record
    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 ...
    View more >
    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.
    View less >
    Journal Title
    Science
    Volume
    365
    Issue
    6460
    DOI
    https://doi.org/10.1126/science.aav7188
    Copyright Statement
    © 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.
    Subject
    Clinical sciences
    Science & Technology
    Multidisciplinary Sciences
    Science & Technology - Other Topics
    GENE-EXPRESSION
    DIAGNOSTIC-CRITERIA
    Publication URI
    http://hdl.handle.net/10072/395033
    Collection
    • Journal articles

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Wang, Zhiquan; Ward, Robert; Warren, James T; Waterman, Richard C; Weikard, Rosemarie; Weinstock, George M; Welsh, Thomas H; Wheeler, David A; Wheeler, Thomas T; White, Stephen N; Whiteside, Matthew D; Wilczek-Boney, Katarzyna; Williams, John L; Williams, Rex Lee; Wilming, Laurens G; Womack, James; Wright, Rita A; Wunderlich, Kris R; Wyss, Carine; Yang, Mary Q; Yang, Jianqi; Zdobnov, Evgeny M; Zhang, Jingkun; Zhao, Feng-Qi; Zhu, Bin (Science, 2009)
      To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven ...
      JOURNAL ARTICLE
    • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis 

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      Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by ...
      JOURNAL ARTICLE

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