The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility
International Multiple Sclerosis Genetics Consortium,
H Bach Sondergaard,
P Soelberg Sorensen,
L Wegner Thoerner,
I Cournu Rebeix,
L Guillot Noel,
C van Duijn,
PWI de Bakker,
P.L. De Jager,
Nicholas A Kennedy,
Mohammed Azam Khan,
Grant W. Montgomery,
Sok Meng Evelyn Ng,
Deborah D. Proctor,
Kirstin M. Taylor,
Johan Van Limbergen,
Andre Van Gossum,
Morten H. Vatn,
Australia and New Zealand IBDGC,
Belgium Genetic Consortium,
Initiative on Crohn and Colitis,
United Kingdom IBDGC,
Wellcome Trust Case Control Consortium
Posted 13 Jul 2017
bioRxiv DOI: 10.1101/143933
Posted 13 Jul 2017
We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish 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 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS 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 do find enrichment for MS genes in these brain-resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.
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