Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility
Articolo
Data di Pubblicazione:
2019
Citazione:
Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility / 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; White, C; Keenan, B; Cimpean, M; Winn, P; Panteliadis, Ip; Robbins, A; Andlauer, Tfm; Zarzycki, O; Dubois, B; Goris, A; Sondergaard, Hb; Sellebjerg, F; Sorensen, Ps; Ullum, H; Thorner, Lw; Saarela, J; Cournu-Rebeix, I; Damotte, V; Fontaine, B; Guillot-Noel, L; Lathrop, M; Vukusic, S; Berthele, A; Pongratz, V; Pongratz, V; Gasperi, C; Graetz, C; Grummel, V; Hemmer, B; Hoshi, M; Knier, B; Korn, T; Lill, Cm; Luessi, F; Muhlau, M; Zipp, F; Dardiotis, E; Agliardi, C; Amoroso, A; Barizzone, N; Benedetti, Md; Bernardinelli, L; Cavalla, P; Clarelli, F; Comi, G; Cusi, D; Esposito, F; Ferre, L; Galimberti, D; Guaschino, C; Leone, Ma; Martinelli, V; Moiola, L; Salvetti, M; Sorosina, M; Vecchio, D; Zauli, A; Santoro, S; Mancini, N; Zuccala, M; Mescheriakova, J; van Duijn, C; Bos, Sd; Celius, Eg; Spurkland, A; Comabella, M; Montalban, X; Alfredsson, L; Bomfim, Il; Gomez-Cabrero, D; Hillert, J; Jagodic, M; Linden, M; Piehl, F; Jelcic, I; Martin, R; Sospedra, M; Baker, A; Ban, M; Hawkins, C; Hysi, P; Kalra, S; Karpe, F; Khadake, J; Lachance, G; Molyneux, P; Neville, M; Thorpe, J; Bradshaw, E; Caillier, Sj; Calabresi, P; Cree, Bac; Cross, A; Davis, M; de Bakker, Pwi; Delgado, S; Dembele, M; Edwards, K; Fitzgerald, K; Frohlich, Iy; Gourraud, Pa; Haines, Jl; Hakonarson, H; Kimbrough, D; Isobe, N; Konidari, I; Lathi, E; Lee, Mh; Li, T; An, D; Zimmer, A; Madireddy, L; Manrique, Cp; Mitrovic, M; Olah, M; Patrick, E; Pericak-Vance, Ma; Piccio, L; Schaefer, C; Weiner, H; Lage, K; Scott, Rj; Lechner-Scott, J; Leal, R; Moscato, P; Booth, Dr; Stewart, Gj; Vucic, S; Pame, G; Bametto, M; Mason, D; Griffiths, L; Broadley, S; Tajouri, L; Baxter, A; Slee, M; Taylor, Bv; Charlesworth, J; Kilpatrick, Tj; Rubio, J; Jokubaitis, V; Wiley, J; Butzkueven, H; Leslie, S; Motyer, A; Stankovich, J; Carroll, Wm; Kermode, Ag; Edrin, M; Barclay, M; Peyrin-Biroulet, L; Chamaillard, M; Colombe, Jf; Cottone, M; Croft, A; D'Inca, R; Halfvarson, J; Hanigan, K; Henderson, P; Hugot, Jp; Karban, A; Kennedy, Na; Khan, Ma; Lemann, M; Levine, A; Massey, D; Milla, M; Motoey, Gw; Ng, Sme; Oikonomnou, J; Peeters, H; Proctor, Dd; Rahier, Jf; Roberts, R; Rutgeerts, P; Seibold, F; Stronati, L; Taylor, Km; Torkvist, L; Ublick, K; Van Limbergen, J; Van Gossum, A; Vatn, Mh; Zhang, H; Zhang, W; Donnelly, P; Barroso, I; Blackwe, Jm; Bramon, E; Brown, Ma; Casas, Jp; Corvin, A; Deloukas, P; Duncanson, A; Jankowski, J; Markus, Hs; Mathew, Cg; Palmer, Cna; Plomin, R; Rautanen, A; Sawcer, Sj; Trembath, Rc; Viswanathan, Ac; Wood, Nw; Spencer, Cca; Band, G; Bellenguez, C; Freeman, C; Hellenthal, G; Giannoulatou, E; Pirinen, M; Pearson, R; Strange, A; Sul, Z; Vukcevic, Da; Donnelly, P; Langford, C; Hunt, Se; Edkins, S; Gwilliam, R; Blackburn, H; Bumpstead, Sj; Dronov, S; Gillman, M; Gray, E; Hammond, N; Jayakumar, A; Mccann, Ot; Liddle, J; Potter, Sc; Ravindrarajah, R; Ricketts, M; Waller, M; Weston, P; Widaa, S; Whittaker, P; Barroso, I; Deloukas, P; Mathew, Cg; Blackwe, Jm; Brown, Ma; Corvin, A; Spencer, Cca; Compston, A; Hafler, D; Harbo, Hf; Hauser, Sl; Stewart, G; D'Alfonso, S; Hadjigeorgiou, G; Taylor, B; Barcellos, Lf; Booth, D; Hintzen, R; Kockum, I; Martinelli-Boneschi, F; Mccauley, Jl; Oksenberg, Jr; Oturai, A; Sawcer, S; Ivinson, Aj; Olsson, T; De Jager, Pl. - In: SCIENCE. - ISSN 0036-8075. - 365:6460(2019), pp. eaav7188-+. [Epub ahead of print] [10.1126/science.aav7188]
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.
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
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; White, C; Keenan, B; Cimpean, M; Winn, P; Panteliadis, Ip; Robbins, A; Andlauer, Tfm; Zarzycki, O; Dubois, B; Goris, A; Sondergaard, Hb; Sellebjerg, F; Sorensen, Ps; Ullum, H; Thorner, Lw; Saarela, J; Cournu-Rebeix, I; Damotte, V; Fontaine, B; Guillot-Noel, L; Lathrop, M; Vukusic, S; Berthele, A; Pongratz, V; Pongratz, V; Gasperi, C; Graetz, C; Grummel, V; Hemmer, B; Hoshi, M; Knier, B; Korn, T; Lill, Cm; Luessi, F; Muhlau, M; Zipp, F; Dardiotis, E; Agliardi, C; Amoroso, A; Barizzone, N; Benedetti, Md; Bernardinelli, L; Cavalla, P; Clarelli, F; Comi, G; Cusi, D; Esposito, F; Ferre, L; Galimberti, D; Guaschino, C; Leone, Ma; Martinelli, V; Moiola, L; Salvetti, M; Sorosina, M; Vecchio, D; Zauli, A; Santoro, S; Mancini, N; Zuccala, M; Mescheriakova, J; van Duijn, C; Bos, Sd; Celius, Eg; Spurkland, A; Comabella, M; Montalban, X; Alfredsson, L; Bomfim, Il; Gomez-Cabrero, D; Hillert, J; Jagodic, M; Linden, M; Piehl, F; Jelcic, I; Martin, R; Sospedra, M; Baker, A; Ban, M; Hawkins, C; Hysi, P; Kalra, S; Karpe, F; Khadake, J; Lachance, G; Molyneux, P; Neville, M; Thorpe, J; Bradshaw, E; Caillier, Sj; Calabresi, P; Cree, Bac; Cross, A; Davis, M; de Bakker, Pwi; Delgado, S; Dembele, M; Edwards, K; Fitzgerald, K; Frohlich, Iy; Gourraud, Pa; Haines, Jl; Hakonarson, H; Kimbrough, D; Isobe, N; Konidari, I; Lathi, E; Lee, Mh; Li, T; An, D; Zimmer, A; Madireddy, L; Manrique, Cp; Mitrovic, M; Olah, M; Patrick, E; Pericak-Vance, Ma; Piccio, L; Schaefer, C; Weiner, H; Lage, K; Scott, Rj; Lechner-Scott, J; Leal, R; Moscato, P; Booth, Dr; Stewart, Gj; Vucic, S; Pame, G; Bametto, M; Mason, D; Griffiths, L; Broadley, S; Tajouri, L; Baxter, A; Slee, M; Taylor, Bv; Charlesworth, J; Kilpatrick, Tj; Rubio, J; Jokubaitis, V; Wiley, J; Butzkueven, H; Leslie, S; Motyer, A; Stankovich, J; Carroll, Wm; Kermode, Ag; Edrin, M; Barclay, M; Peyrin-Biroulet, L; Chamaillard, M; Colombe, Jf; Cottone, M; Croft, A; D'Inca, R; Halfvarson, J; Hanigan, K; Henderson, P; Hugot, Jp; Karban, A; Kennedy, Na; Khan, Ma; Lemann, M; Levine, A; Massey, D; Milla, M; Motoey, Gw; Ng, Sme; Oikonomnou, J; Peeters, H; Proctor, Dd; Rahier, Jf; Roberts, R; Rutgeerts, P; Seibold, F; Stronati, L; Taylor, Km; Torkvist, L; Ublick, K; Van Limbergen, J; Van Gossum, A; Vatn, Mh; Zhang, H; Zhang, W; Donnelly, P; Barroso, I; Blackwe, Jm; Bramon, E; Brown, Ma; Casas, Jp; Corvin, A; Deloukas, P; Duncanson, A; Jankowski, J; Markus, Hs; Mathew, Cg; Palmer, Cna; Plomin, R; Rautanen, A; Sawcer, Sj; Trembath, Rc; Viswanathan, Ac; Wood, Nw; Spencer, Cca; Band, G; Bellenguez, C; Freeman, C; Hellenthal, G; Giannoulatou, E; Pirinen, M; Pearson, R; Strange, A; Sul, Z; Vukcevic, Da; Donnelly, P; Langford, C; Hunt, Se; Edkins, S; Gwilliam, R; Blackburn, H; Bumpstead, Sj; Dronov, S; Gillman, M; Gray, E; Hammond, N; Jayakumar, A; Mccann, Ot; Liddle, J; Potter, Sc; Ravindrarajah, R; Ricketts, M; Waller, M; Weston, P; Widaa, S; Whittaker, P; Barroso, I; Deloukas, P; Mathew, Cg; Blackwe, Jm; Brown, Ma; Corvin, A; Spencer, Cca; Compston, A; Hafler, D; Harbo, Hf; Hauser, Sl; Stewart, G; D'Alfonso, S; Hadjigeorgiou, G; Taylor, B; Barcellos, Lf; Booth, D; Hintzen, R; Kockum, I; Martinelli-Boneschi, F; Mccauley, Jl; Oksenberg, Jr; Oturai, A; Sawcer, S; Ivinson, Aj; Olsson, T; De Jager, Pl
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