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

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@article{0fca40a1d1e740d8923357bdcd762519,
title = "Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility",
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.",
author = "{International Multiple Sclerosis Genetics Consortium} and Henrik Ullum and Th{\o}rner, {Lise Wegner} and Sellebjerg, {Finn Thorup} and S{\o}rensen, {Per Soelberg}",
note = "Copyright {\textcopyright} 2019, American Association for the Advancement of Science.",
year = "2019",
month = sep,
day = "27",
doi = "10.1126/science.aav7188",
language = "English",
volume = "365",
pages = "eaav7188",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6460",

}

RIS

TY - JOUR

T1 - Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

AU - International Multiple Sclerosis Genetics Consortium

A2 - Ullum, Henrik

A2 - Thørner, Lise Wegner

A2 - Sellebjerg, Finn Thorup

A2 - Sørensen, Per Soelberg

N1 - Copyright © 2019, American Association for the Advancement of Science.

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.

U2 - 10.1126/science.aav7188

DO - 10.1126/science.aav7188

M3 - Journal article

C2 - 31604244

VL - 365

SP - eaav7188

JO - Science

JF - Science

SN - 0036-8075

IS - 6460

ER -

ID: 58975645