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 journalArticlepeer-review


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
Issue number6460
Publication statusPublished - Sep 27 2019


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