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

International Multiple Sclerosis Genetics Consortium, ANZgene, IIBDGC, WTCCC2

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbereaav7188
JournalScience
Volume365
Issue number6460
DOIs
StatePublished - Sep 27 2019

Fingerprint

Microglia
Multiple Sclerosis
Major Histocompatibility Complex
X Chromosome
Genes
Immune System
Central Nervous System
Brain

ASJC Scopus subject areas

  • General

Cite this

International Multiple Sclerosis Genetics Consortium, & ANZgene, IIBDGC, WTCCC2 (2019). Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science, 365(6460), [eaav7188]. https://doi.org/10.1126/science.aav7188

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. / International Multiple Sclerosis Genetics Consortium; ANZgene, IIBDGC, WTCCC2.

In: Science, Vol. 365, No. 6460, eaav7188, 27.09.2019.

Research output: Contribution to journalArticle

International Multiple Sclerosis Genetics Consortium & ANZgene, IIBDGC, WTCCC2 2019, 'Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility', Science, vol. 365, no. 6460, eaav7188. https://doi.org/10.1126/science.aav7188
International Multiple Sclerosis Genetics Consortium, ANZgene, IIBDGC, WTCCC2. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019 Sep 27;365(6460). eaav7188. https://doi.org/10.1126/science.aav7188
International Multiple Sclerosis Genetics Consortium ; ANZgene, IIBDGC, WTCCC2. / Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. In: Science. 2019 ; Vol. 365, No. 6460.
@article{2afe2849ed4d4a2a8b860d3de58078f4,
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 {ANZgene, IIBDGC, WTCCC2} and Patsopoulos, {Nikolaos A.} and Baranzini, {Sergio E.} and Adam Santaniello and Parisa Shoostari and Chris Cotsapas and Garrett Wong and Beecham, {Ashley H.} and Tojo James and Joseph Replogle and Vlachos, {Ioannis S.} and Cristin McCabe and Pers, {Tune H.} and Aaron Brandes and Charles White and Brendan Keenan and Maria Cimpean and Phoebe Winn and Panteliadis, {Ioannis Pavlos} and Allison Robbins and Andlauer, {Till F.M.} and Onigiusz Zarzycki and B{\'e}n{\'e}dicte Dubois and An Goris and S{\o}ndergaard, {Helle Bach} and Finn Sellebjerg and Sorensen, {Per Soelberg} and Henrik Ullum and Th{\o}rner, {Lise Wegner} and Janna Saarela and Isabelle Cournu-Rebeix and Vincent Damotte and Bertrand Fontaine and Lena Guillot-Noel and Mark Lathrop and Sandra Vukusic and Achim Berthele and Viola Pongratz and Dorothea Buck and Christiane Gasperi and Christiane Graetz and Verena Grummel and Bernhard Hemmer and Muni Hoshi and Benjamin Knier and Thomas Korn and Lill, {Christina M.} and Felix Luessi and Mark M{\"u}hlau and Peter Calabresi and Kate Fitzgerald",
year = "2019",
month = "9",
day = "27",
doi = "10.1126/science.aav7188",
language = "English (US)",
volume = "365",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6460",

}

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 - Calabresi, Peter

AU - Fitzgerald, Kate

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

UR - http://www.scopus.com/inward/citedby.url?scp=85072692374&partnerID=8YFLogxK

U2 - 10.1126/science.aav7188

DO - 10.1126/science.aav7188

M3 - Article

C2 - 31604244

AN - SCOPUS:85072692374

VL - 365

JO - Science

JF - Science

SN - 0036-8075

IS - 6460

M1 - eaav7188

ER -