The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
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多发性硬化症基因组图谱：外周免疫细胞和常驻小胶质细胞在易感性中的作用
DOI：
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Wei Zhang
中科院分区：
文献类型：
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作者：
N. Patsopoulos;S. Baranzini;A. Santaniello;P. Shoostari;C. Cotsapas;G. Wong;A. Beecham;T. James;J. Replogle;I. Vlachos;C. McCabe;T. Pers;A. Brandes;C. White;B. Keenan;M. Cimpean;P. Winn;I. Panteliadis;A. Robbins;T. Andlauer;O. Zarzycki;B. Dubois;A. Goris;H. Søndergaard;F. Sellebjerg;P. Sørensen;H. Ullum;L. W. Thoerner;J. Saarela;I. Rebeix;V. Damotte;B. Fontaine;L. Noel;M. Lathrop;S. Vukusik;A. Berthele;V. Biberacher;D. Buck;C. Gasperi;C. Graetz;V. Grummel;B. Hemmer;M. Hoshi;B. Knier;T. Korn;C. Lill;F. Luessi;M. Mühlau;F. Zipp;E. Dardiotis;C. Agliardi;A. Amoroso;N. Barizzone;M. Benedetti;L. Bernardinelli;P. Cavalla;F. Clarelli;G. Comi;D. Cusi;F. Esposito;L. Ferré;D. Galimberti;C. Guaschino;M. Leone;V. Martinelli;L. Moiola;M. Salvetti;M. Sorosina;D. Vecchio;A. Zauli;S. Santoro;M. Zuccalà;J. Mescheriakova;C. Duijn;S. Bos;E. Celius;A. Spurkland;M. Comabella;X. Montalban;L. Alfredsson;I. Bomfim;D. Gómez;J. Hillert;M. Jagodic;M. Lindén;F. Piehl;I. Jelcic;R. Martin;M. Sospedra;A. Baker;M. Ban;C. Hawkins;P. Hysi;S. Kalra;F. Karpe;J. Khadake;G. Lachance;P. Molyneux;M. Neville;J. Thorpe;E. Bradshaw;S. Caillier;P. Calabresi;B. Cree;A. Cross;M. Davis;P. D. Bakker;S. Delgado;M. Dembele;K. Edwards;K. Fitzgerald;I. Frohlich;P. Gourraud;J. Haines;H. Hakonarson;D. Kimbrough;N. Isobe;I. Konidari;E. Lathi;MH Lee;T. Li;D. An;A. Zimmer;A. Lo;L. Madireddy;C. Manrique;M. Mitrovič;M. Olah;E. Patrick;M. Pericak;L. Piccio;C. Schaefer;H. Weiner;K. Lage;A. Compston;D. Hafler;H. Harbo;S. Hauser;G. Stewart;S. D'alfonso;G. Hadjigeorgiou;B. Taylor;L. Barcellos;D. Booth;R. Hintzen;I. Kockum;F. Martinelli;J. McCauley;J. Oksenberg;A. Oturai;S. Sawcer;A. Ivinson;T. Olsson;P. D. Jager;M. Barclay;L. Peyrin;M. Chamaillard;J. Colombe;M. Cottone;A. Croft;R. D'Incà;J. Halfvarson;K. Hanigan;P. Henderson;J. Hugot;A. Karban;N. Kennedy;M. Khan;M. Lémann;A. Levine;D. Massey;M. Milla;G. Montgomery;Sok Meng Evelyn Ng;I. Oikonomou;H. Peeters;D. Proctor;J. Rahier;R. Roberts;P. Rutgeerts;F. Seibold;L. Stronati;K. Taylor;L. Törkvist;Kullak Ublick;J. V. Limbergen;A. Gossum;M. Vatn;Hu Zhang;Wei Zhang
我们收集并分析了47，351例多发性硬化（MS）受试者和68，284例对照受试者的遗传数据，并建立了MS遗传结构的参考图谱，其中包括主要组织相容性复合体（MHC）外的200个常染色体易感性变异，一个X染色体变异和扩展MHC内的32个独立关联。我们使用了一系列方法来优先考虑多达551个潜在相关的MS易感基因，这些基因涉及分布在免疫系统细胞组分中的多种先天和适应性途径。使用纯化的人类小胶质细胞的表达谱，我们确实发现MS基因在这些脑驻留免疫细胞中富集。因此，虽然MS最初很可能是由外周免疫反应的扰动触发的，但小胶质细胞和其他脑细胞的功能反应也发生了改变，并且可能在将自身免疫过程靶向中枢神经系统中发挥作用。一句话总结：我们报告了多发性硬化症的详细的遗传和基因组图谱，并描述了外周免疫系统和脑内小胶质细胞中受pupillary影响的基因的作用。
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.
影响因子：
9.8
作者：
Hu, Xinli;Kim, Hyun;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya
影响因子：
64.8
作者：
Sawcer, Stephen;Hellenthal, Garrett;Pirinen, Matti;Spencer, Chris C. A.;Patsopoulos, Nikolaos A.;Moutsianas, Loukas;Dilthey, Alexander;Su, Zhan;Freeman, Colin;Hunt, Sarah E.;Edkins, Sarah;Gray, Emma;Booth, David R.;Potter, Simon C.;Goris, An;Band, Gavin;Oturai, Annette Bang;Strange, Amy;Saarela, Janna;Bellenguez, Celine;Fontaine, Bertrand;Gillman, Matthew;Hemmer, Bernhard;Gwilliam, Rhian;Zipp, Frauke;Jayakumar, Alagurevathi;Martin, Roland;Leslie, Stephen;Hawkins, Stanley;Giannoulatou, Eleni;D'alfonso, Sandra;Blackburn, Hannah;Boneschi, Filippo Martinelli;Liddle, Jennifer;Harbo, Hanne F.;Perez, Marc L.;Spurkland, Anne;Waller, Matthew J.;Mycko, Marcin P.;Ricketts, Michelle;Comabella, Manuel;Hammond, Naomi;Kockum, Ingrid;McCann, Owen T.;Ban, Maria;Whittaker, Pamela;Kemppinen, Anu;Weston, Paul;Hawkins, Clive;Widaa, Sara;Zajicek, John;Dronov, Serge;Robertson, Neil;Bumpstead, Suzannah J.;Barcellos, Lisa F.;Ravindrarajah, Rathi;Abraham, Roby;Alfredsson, Lars;Ardlie, Kristin;Aubin, Cristin;Baker, Amie;Baker, Katharine;Baranzini, Sergio E.;Bergamaschi, Laura;Bergamaschi, Roberto;Bernstein, Allan;Berthele, Achim;Boggild, Mike;Bradfield, Jonathan P.;Brassat, David;Broadley, Simon A.;Buck, Dorothea;Butzkueven, Helmut;Capra, Ruggero;Carroll, William M.;Cavalla, Paola;Celius, Elisabeth G.;Cepok, Sabine;Chiavacci, Rosetta;Clerget-Darpoux, Francoise;Clysters, Katleen;Comi, Giancarlo;Cossburn, Mark;Cournu-Rebeix, Isabelle;Cox, Mathew B.;Cozen, Wendy;Cree, Bruce A. C.;Cross, Anne H.;Cusi, Daniele;Daly, Mark J.;Davis, Emma;de Bakker, Paul I. W.;Debouverie, Marc;D'hooghe, Marie Beatrice;Dixon, Katherine;Dobosi, Rita;Dubois, Benedicte;Ellinghaus, David;Elovaara, Irina;Esposito, Federica;Fontenille, Claire;Foote, Simon;Franke, Andre;Galimberti, Daniela;Ghezzi, Angelo;Glessner, Joseph;Gomez, Refujia;Gout, Olivier;Graham, Colin;Grant, Struan F. A.;Guerini, Franca Rosa;Hakonarson, Hakon;Hall, Per;Hamsten, Anders;Hartung, Hans-Peter;Heard, Rob N.;Heath, Simon;Hobart, Jeremy;Hoshi, Muna;Infante-Duarte, Carmen;Ingram, Gillian;Ingram, Wendy;Islam, Talat;Jagodic, Maja;Kabesch, Michael;Kermode, Allan G.;Kilpatrick, Trevor J.;Kim, Cecilia;Klopp, Norman;Koivisto, Keijo;Larsson, Malin;Lathrop, Mark;Lechner-Scott, Jeannette S.;Leone, Maurizio A.;Leppa, Virpi;Liljedahl, Ulrika;Bomfim, Izaura Lima;Lincoln, Robin R.;Link, Jenny;Liu, Jianjun;Lorentzen, Aslaug R.;Lupoli, Sara;Macciardi, Fabio;Mack, Thomas;Marriott, Mark;Martinelli, Vittorio;Mason, Deborah;McCauley, Jacob L.;Mentch, Frank;Mero, Inger-Lise;Mihalova, Tania;Montalban, Xavier;Mottershead, John;Myhr, Kjell-Morten;Naldi, Paola;Ollier, William;Page, Alison;Palotie, Aarno;Pelletier, Jean;Piccio, Laura;Pickersgill, Trevor;Piehl, Fredrik;Pobywajlo, Susan;Quach, Hong L.;Ramsay, Patricia P.;Reunanen, Mauri;Reynolds, Richard;Rioux, Johnd.;Rodegher, Mariaemma;Roesner, Sabine;Rubio, Justin P.;Rueckert, Ina-Maria;Salvetti, Marco;Salvi, Erika;Santaniello, Adam;Schaefer, Catherine A.;Schreiber, Stefan;Schulze, Christian;Scott, Rodney J.;Sellebjerg, Finn;Selmaj, Krzysztof W.;Sexton, David;Shen, Ling;Simms-Acuna, Brigid;Skidmore, Sheila;Sleiman, Patrick M. A.;Smestad, Cathrine;Sorensen, Per Soelberg;Sondergaard, Helle Bach;Stankovich, Jim;Strange, Richard C.;Sulonen, Anna-Maija;Sundqvist, Emilie;Syvaenen, Ann-Christine;Taddeo, Francesca;Taylor, Bruce;Blackwell, Jenefer M.;Tienari, Pentti;Bramon, Elvira;Tourbah, Ayman;Brown, Matthew A.;Tronczynska, Ewa;Casas, Juan P.;Tubridy, Niall;Corvin, Aiden;Vickery, Jane;Jankowski, Janusz;Villoslada, Pablo;Markus, Hugh S.;Wang, Kai;Mathew, Christopher G.;Wason, James;Palmer, Colin N. A.;Wichmann, H-Erich;Plomin, Robert;Willoughby, Ernest;Rautanen, Anna;Winkelmann, Juliane;Wittig, Michael;Trembath, Richard C.;Yaouanq, Jacqueline;Viswanathan, Ananth C.;Zhang, Haitao;Wood, Nicholas W.;Zuvich, Rebecca;Deloukas, Panos;Langford, Cordelia;Duncanson, Audrey;Oksenberg, Jorge R.;Pericak-Vance, Margaret A.;Haines, Jonathan L.;Olsson, Tomas;Hillert, Jan;Ivinson, Adrian J.;De Jager, Philip L.;Peltonen, Leena;Stewart, Graeme J.;Hafler, David A.;Hauser, Stephen L.;McVean, Gil;Donnelly, Peter;Compston, Alastair
通讯作者：
Compston, Alastair
影响因子：
158.5
作者：
Hafler, David A.;Compston, Alastair;Hauser, Stephen L.
通讯作者：
Hauser, Stephen L.