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

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 w...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 365; no. 6460
Format: Journal Article
Language:English
Published: United States 27.09.2019
Subjects:
Case-Control Studies
Cell Cycle Proteins - genetics
Chromosome Mapping
Chromosomes, Human, X - genetics
Gene Frequency
Genetic Loci
Genome-Wide Association Study
Genomics
GTPase-Activating Proteins - genetics
Humans
Inheritance Patterns
Major Histocompatibility Complex
Microglia - immunology
Multiple Sclerosis - genetics
Polymorphism, Single Nucleotide
Quantitative Trait Loci
RNA-Seq
Transcriptome
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary: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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ISSN:1095-9203
1095-9203
DOI:10.1126/science.aav7188