Multiple Sclerosis Genomic Map implicates peripheral immune cells & microglia in susceptibility

作者：N. A. Patsopoulos, N. A. Patsopoulos, S. Baranzini, A. Santaniello, P. Shoostari, C. Cotsapas, G. Wong, Ashley H Beecham, T. James, J. Replogle, I. Vlachos, C. McCabe, T. Pers, T. Pers, A. Brandes, C. White, B. Keenan, M. Cimpean, P. Winn, Ioannis-Pavlos Panteliadis, A. Robbins, Till F. M. Andlauer, O. Zarzycki, B. Dubois, A. Goris, H. Søndergaard, F. Sellebjerg, P. Sørensen, H. Ullum, L. Thørner, J. Saarela, I. Cournu-Rebeix, V. Damotte, B. Fontaine, L. Guillot-Noel, M. Lathrop, S. Vukusic, A. Berthele, Viola Pongratz, C. Gasperi, C. Graetz, V. Grummel, B. Hemmer, Muni Hoshi, B. Knier, T. Korn, C. Lill, F. Luessi, M. Muehlau, 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, N. Mancini, M. Zuccalà, J. Mescheriakova, C. Duijn, S. Bos, E. Celius, A. Spurkland, M. Comabella, X. Montalban, L. Alfredsson, I. Bomfim, D. Gómez-Cabrero, J. Hillert, M. Jagodic, M. Lindén, F. Piehl, I. Jelcic, Roland 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, Stacy J Caillier, P. Calabresi, B. Cree, A. Cross, Mary F. 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, Michelle H. Lee, Tai-an Li, D. An, A. Zimmer, L. Madireddy, C. Manrique, M. Mitrovič, M. Olah, E. Patrick, M. Pericak-Vance, L. Piccio, C. Schaefer, H. Weiner, K. Lage, R. Scott, J. Lechner-Scott, R. Leal, P. Moscato, D. Booth, G. Stewart, S. Vucic, Grant Pame, Michael BamettO, D. Mason, L. Griffiths, S. Broadley, L. Tajouri, A. Baxter, M. Slee, B. Taylor, J. Charlesworth, T. Kilpatrick, J. Rubio, V. Jokubaitis, J. Wiley, H. Butzkueven, S. Leslie, A. Motyer, J. Stankovich, W. Carroll, A. Kermode, Marzena Edrin, M. Barclay, L. Peyrin-Biroulet, 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, Grant W. Motoey, S. M. Ng, Joannis Oikonomnou, 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, P. Donnelly, I. Barroso, Jenefer M. Blackwe, E. Bramon, M. Brown, J. Casas, A. Corvin, P. Deloukas, A. Duncanson, Janusz Jankowski, H. Markus, C. Mathew, C. Palmer, R. Plomin, A. Rautanen, S. Sawcer, R. Trembath, A. Viswanathan, N. Wood, C. Spencer, G. Band, C. Bellenguez, C. Freeman, G. Hellenthal, E. Giannoulatou, M. Pirinen, R. Pearson, A. Strange, Zhan Sul, Damjan Vukcevic, C. Langford, S. Hunt, S. Edkins, R. Gwilliam, H. Blackburn, S. Bumpstead, S. Dronov, M. Gillman, Emma V. Gray, Naomi Hammond, Alagurevathi Jayakumar, O. Mccann, J. Liddle, Simon C. Potter, Radhi Ravindrarajah, M. Ricketts, M. Waller, P. Weston, S. Widaa, P. Whittaker, Alastair Compston, D. Hafler, H. Harbo, S. Hauser, G. Stewart, S. D'alfonso, G. Hadjigeorgiou, B. E. Taylor, L. Barcellos, D. Booth, R. Hintzen, I. Kockum, F. Martinelli-Boneschi, Jacob L. McCauley, J. Oksenberg, A. Oturai, S. Sawcer, A. Ivinson, T. Olsson, P. Jager · 发表于：Science · 年份：2019 · DOI：10.1126/science.aav7188 · 被引用次数：1196 · 研究领域：Biology、Medicine

Genetic roots of multiple sclerosis The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis. Science, this issue p. eaav7188; see also p. 1383 A genomic map of multiple sclerosis identifies putatively affected immune genes. INTRODUCTION Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) that often presents in young adults. Over the past decade, certain elements of the genetic architecture of susceptibility have gradually emerged, but most of the genetic risk for MS remained unknown. RATIONALE Earlier versions of the MS genetic map had highlighted the role of the adaptive arm of the immune system, implicating multiple different T cell subsets. We expanded our knowledge of MS susceptibility by performing a...