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

International Multiple Sclerosis Genetics Consortium; ANZgene, IIBDGC, WTCCC2

doi:10.1126/science.aav7188

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

International Multiple Sclerosis Genetics Consortium
, ANZgene, IIBDGC, WTCCC2

Brigham and Women's Hospital
Harvard Medical School
Massachusetts Institute of Technology (MIT)
University of California San Francisco
Yale University Medical School
Hospital for Sick Children and University of Toronto
University of Miami Miller School of Medicine
Karolinska Institutet
Columbia University Irving Medical Center
Novo Nordisk Foundation Center for Basic Metabolic Research
University of Pennsylvania
Max Planck Institute of Psychiatry
Technische Universität München
German Competence Network Multiple Sclerosis (KKNMS)
University of Leuven
University of Copenhagen
University of Helsinki
Centre de Recherche Institut du Cerveau et de la Moelle
CHRU Roger Salengro
AP-HP
Centre National de Genotypage
Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain
McGill University
Hospices Civils de Lyon
Lyon Neuroscience Research Center
Université Claude Bernard Lyon 1
Eugène Devic EDMUS Foundation against multiple sclerosis
University Medical Center
Munich Cluster for Systems Neurology (SyNergy)
University of Lübeck
University Hospital of Larissa
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Maria Nascente
University of Torino
University of Eastern Piedmont
Azienda Ospedaliera Universitaria Integrata Verona
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Cambridge Biomedical Campus
University of Torino
IRCCS San Raffaele Scientific Institute
University of Milan, DISAA
Istituto di Ricovero e Cura A Carattere Scientifico-Casa Sollievo della Sofferenza Hospital
Universita La Sapienza
IRCCS Neuromed
AOU Maggiore della Carità
Erasmus MC
University of Oxford
University of Oslo
Oslo University Hospital
Hospital Universitari Vall d’Hebron
Universidad Pública de Navarra
King's College London
University Hospital Zurich
Department of Clinical Neurosciences
Keele University Medical School
Churchill Hospital
University of Cambridge
Peterborough City Hospital
Johns Hopkins School of Medicine
Washington University in St. Louis
Vanderbilt School of Medicine
Vertex Pharmaceuticals, Inc.
MS Center of Northeastern NY
l'institut du thorax
Case Western Reserve University School of Medicine
Children's Hospital of Philadelphia
Graduate School of Medical Sciences
Elliot Lewis Center
Broad Institute of Harvard and MIT
University of Sydney
Kaiser Permanente Division of Research
University of Tasmania
University of California at Berkeley

Publikation: Beitrag in Fachzeitschrift › Artikel › Begutachtung

1163 Zitate (Scopus)

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.

Originalsprache	Englisch
Aufsatznummer	eaav7188
Fachzeitschrift	Science
Jahrgang	365
Ausgabenummer	6460
DOIs	https://doi.org/10.1126/science.aav7188
Publikationsstatus	Veröffentlicht - 27 Sept. 2019

Zugriff auf Dokument

10.1126/science.aav7188

Andere Dateien und Links

Verknüpfung zur Publikation in Scopus

Dieses zitieren

@article{40f2b6680e7e4abd9199ce8f28adff6d,

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 Frauke Zipp and Efthimios Dardiotis",

year = "2019",

month = sep,

day = "27",

doi = "10.1126/science.aav7188",

language = "English",

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 - Zipp, Frauke

AU - Dardiotis, Efthimios

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 - https://www.scopus.com/pages/publications/85072692374

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 -

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

Abstract

Zugriff auf Dokument

Andere Dateien und Links

Fingerprint

Dieses zitieren