TY - JOUR
T1 - Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility
AU - International Multiple Sclerosis Genetics Consortium
AU - ANZgene, IIBDGC, WTCCC2
AU - Patsopoulos, Nikolaos A.
AU - Baranzini, Sergio E.
AU - Santaniello, Adam
AU - Shoostari, Parisa
AU - Cotsapas, Chris
AU - Wong, Garrett
AU - Beecham, Ashley H.
AU - James, Tojo
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 - Pongratz, Viola
AU - Buck, Dorothea
AU - Gasperi, Christiane
AU - Graetz, Christiane
AU - Grummel, Verena
AU - Hemmer, Bernhard
AU - Hoshi, Muni
AU - Knier, Benjamin
AU - Korn, Thomas
AU - Lill, Christina M.
AU - Luessi, Felix
AU - Mühlau, Mark
AU - Cross, Anne
AU - Piccio, Laura
N1 - Publisher Copyright:
© 2019 American Association for the Advancement of Science. All rights reserved.
PY - 2019/9/27
Y1 - 2019/9/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072692374&partnerID=8YFLogxK
U2 - 10.1126/science.aav7188
DO - 10.1126/science.aav7188
M3 - Article
C2 - 31604244
AN - SCOPUS:85072692374
SN - 0036-8075
VL - 365
JO - Science
JF - Science
IS - 6460
M1 - eaav7188
ER -