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

International Multiple Sclerosis Genetics Consortium, WTCCC2 ANZgene IIBDGC, Nikolaos A. Patsopoulos, Sergio E. Baranzini, Adam Santaniello, Parisa Shoostari, Chris Cotsapas, Garrett Wong, Ashley H. Beecham, Tojo James, Joseph Replogle, Ioannis S. Vlachos, Cristin McCabe, Tune H. Pers, Aaron Brandes, Charles White, Brendan Keenan, Maria Cimpean, Phoebe Winn, Ioannis Pavlos PanteliadisAllison Robbins, Till F.M. Andlauer, Onigiusz Zarzycki, Bénédicte Dubois, An Goris, Helle Bach Søndergaard, Finn Sellebjerg, Per Soelberg Sorensen, Henrik Ullum, Lise Wegner Thørner, Janna Saarela, Isabelle Cournu-Rebeix, Vincent Damotte, Bertrand Fontaine, Lena Guillot-Noel, Mark Lathrop, Sandra Vukusic, Achim Berthele, Cristina Agliardi, Ferdinando Clarelli, Giancarlo Comi, Federica Esposito, Laura Ferrè, Daniela Galimberti, Maurizio A. Leone, Vittorio Martinelli, Lucia Moiola, Marco Salvetti, Melissa Sorosina, Silvia Santoro, Nicasio Mancini, Filippo Martinelli-Boneschi

Research output: Contribution to journalArticle

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.
Original languageEnglish
JournalScience
Volume365
Issue number6460
DOIs
Publication statusPublished - Sep 27 2019

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Microglia
Multiple Sclerosis
Major Histocompatibility Complex
X Chromosome
Genes
Immune System
Central Nervous System
Brain

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Consortium, I. M. S. G., ANZgene IIBDGC, WTCCC., Patsopoulos, N. A., Baranzini, S. E., Santaniello, A., Shoostari, P., ... Martinelli-Boneschi, F. (2019). Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science, 365(6460). https://doi.org/10.1126/science.aav7188

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. / Consortium, International Multiple Sclerosis Genetics; ANZgene IIBDGC, WTCCC2; Patsopoulos, Nikolaos A.; Baranzini, Sergio E.; Santaniello, Adam; 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 F.M.; Zarzycki, Onigiusz; Dubois, Bénédicte; Goris, An; Søndergaard, Helle Bach; Sellebjerg, Finn; Sorensen, Per Soelberg; Ullum, Henrik; Thørner, Lise Wegner; Saarela, Janna; Cournu-Rebeix, Isabelle; Damotte, Vincent; Fontaine, Bertrand; Guillot-Noel, Lena; Lathrop, Mark; Vukusic, Sandra; Berthele, Achim; Agliardi, Cristina; Clarelli, Ferdinando; Comi, Giancarlo; Esposito, Federica; Ferrè, Laura; Galimberti, Daniela; Leone, Maurizio A.; Martinelli, Vittorio; Moiola, Lucia; Salvetti, Marco; Sorosina, Melissa; Santoro, Silvia; Mancini, Nicasio; Martinelli-Boneschi, Filippo.

In: Science, Vol. 365, No. 6460, 27.09.2019.

Research output: Contribution to journalArticle

Consortium, IMSG, ANZgene IIBDGC, WTCCC, 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, Søndergaard, HB, Sellebjerg, F, Sorensen, PS, Ullum, H, Thørner, LW, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Agliardi, C, Clarelli, F, Comi, G, Esposito, F, Ferrè, L, Galimberti, D, Leone, MA, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Santoro, S, Mancini, N & Martinelli-Boneschi, F 2019, 'Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility', Science, vol. 365, no. 6460. https://doi.org/10.1126/science.aav7188
Consortium IMSG, ANZgene IIBDGC WTCCC, Patsopoulos NA, Baranzini SE, Santaniello A, Shoostari P et al. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019 Sep 27;365(6460). https://doi.org/10.1126/science.aav7188
Consortium, International Multiple Sclerosis Genetics ; ANZgene IIBDGC, WTCCC2 ; Patsopoulos, Nikolaos A. ; Baranzini, Sergio E. ; Santaniello, Adam ; 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 F.M. ; Zarzycki, Onigiusz ; Dubois, Bénédicte ; Goris, An ; Søndergaard, Helle Bach ; Sellebjerg, Finn ; Sorensen, Per Soelberg ; Ullum, Henrik ; Thørner, Lise Wegner ; Saarela, Janna ; Cournu-Rebeix, Isabelle ; Damotte, Vincent ; Fontaine, Bertrand ; Guillot-Noel, Lena ; Lathrop, Mark ; Vukusic, Sandra ; Berthele, Achim ; Agliardi, Cristina ; Clarelli, Ferdinando ; Comi, Giancarlo ; Esposito, Federica ; Ferrè, Laura ; Galimberti, Daniela ; Leone, Maurizio A. ; Martinelli, Vittorio ; Moiola, Lucia ; Salvetti, Marco ; Sorosina, Melissa ; Santoro, Silvia ; Mancini, Nicasio ; Martinelli-Boneschi, Filippo. / Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. In: Science. 2019 ; Vol. 365, No. 6460.
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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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AU - Consortium, International Multiple Sclerosis Genetics

AU - ANZgene IIBDGC, WTCCC2

AU - Patsopoulos, Nikolaos A.

AU - Baranzini, Sergio E.

AU - Santaniello, Adam

AU - Shoostari, Parisa

AU - Cotsapas, Chris

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AU - Beecham, Ashley H.

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AU - Replogle, Joseph

AU - Vlachos, Ioannis S.

AU - McCabe, Cristin

AU - Pers, Tune H.

AU - Brandes, Aaron

AU - White, Charles

AU - Keenan, Brendan

AU - Cimpean, Maria

AU - Winn, Phoebe

AU - Panteliadis, Ioannis Pavlos

AU - Robbins, Allison

AU - Andlauer, Till F.M.

AU - Zarzycki, Onigiusz

AU - Dubois, Bénédicte

AU - Goris, An

AU - Søndergaard, Helle Bach

AU - Sellebjerg, Finn

AU - Sorensen, Per Soelberg

AU - Ullum, Henrik

AU - Thørner, Lise Wegner

AU - Saarela, Janna

AU - Cournu-Rebeix, Isabelle

AU - Damotte, Vincent

AU - Fontaine, Bertrand

AU - Guillot-Noel, Lena

AU - Lathrop, Mark

AU - Vukusic, Sandra

AU - Berthele, Achim

AU - Agliardi, Cristina

AU - Clarelli, Ferdinando

AU - Comi, Giancarlo

AU - Esposito, Federica

AU - Ferrè, Laura

AU - Galimberti, Daniela

AU - Leone, Maurizio A.

AU - Martinelli, Vittorio

AU - Moiola, Lucia

AU - Salvetti, Marco

AU - Sorosina, Melissa

AU - Santoro, Silvia

AU - Mancini, Nicasio

AU - Martinelli-Boneschi, Filippo

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DO - 10.1126/science.aav7188

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