2019
Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility
Patsopoulos N, Baranzini S, Santaniello A, Shoostari P, Cotsapas C, Wong G, Beecham A, James T, Replogle J, Vlachos I, McCabe C, Pers T, Brandes A, White C, Keenan B, Cimpean M, Winn P, Panteliadis I, Robbins A, Andlauer T, Zarzycki O, Dubois B, Goris A, Søndergaard H, Sellebjerg F, Sorensen P, Ullum H, Thørner L, Saarela J, Cournu-Rebeix I, Damotte V, Fontaine B, Guillot-Noel L, Lathrop M, Vukusic S, Berthele A, Pongratz V, Buck D, Gasperi C, Graetz C, Grummel V, Hemmer B, Hoshi M, Knier B, Korn T, Lill C, Luessi F, Mühlau M, Zipp F, Dardiotis E, Agliardi C, Amoroso A, Barizzone N, Benedetti M, Bernardinelli L, Cavalla P, Clarelli F, Comi G, Cusi D, Esposito F, Ferrè L, Galimberti D, Guaschino C, Leone M, Martinelli V, Moiola L, Salvetti M, Sorosina M, Vecchio D, Zauli A, Santoro S, Mancini N, Zuccalà M, Mescheriakova J, van Duijn C, Bos S, Celius E, Spurkland A, Comabella M, Montalban X, Alfredsson L, Bomfim I, Gomez-Cabrero D, Hillert J, Jagodic M, Lindén M, Piehl F, Jelčić I, Martin R, Sospedra M, Baker A, Ban M, Hawkins C, Hysi P, Kalra S, Karpe F, Khadake J, Lachance G, Molyneux P, Neville M, Thorpe J, Bradshaw E, Caillier S, Calabresi P, Cree B, Cross A, Davis M, de Bakker P, Delgado S, Dembele M, Edwards K, Fitzgerald K, Frohlich I, Gourraud P, Haines J, Hakonarson H, Kimbrough D, Isobe N, Konidari I, Lathi E, Lee M, Li T, An D, Zimmer A, Madireddy L, Manrique C, Mitrovic M, Olah M, Patrick E, Pericak-Vance M, Piccio L, Schaefer C, Weiner H, Lage K, Compston A, Hafler D, Harbo H, Hauser S, Stewart G, D’Alfonso S, Hadjigeorgiou G, Taylor B, Barcellos L, Booth D, Hintzen R, Kockum I, Martinelli-Boneschi F, McCauley J, Oksenberg J, Oturai A, Sawcer S, Ivinson A, Olsson T, De Jager P. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 2019, 365 PMID: 31604244, PMCID: PMC7241648, DOI: 10.1126/science.aav7188.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCell Cycle ProteinsChromosome MappingChromosomes, Human, XGene FrequencyGenetic LociGenome-Wide Association StudyGenomicsGTPase-Activating ProteinsHumansInheritance PatternsMajor Histocompatibility ComplexMicrogliaMultiple SclerosisPolymorphism, Single NucleotideQuantitative Trait LociRNA-SeqTranscriptomeConceptsMajor histocompatibility complexMultiple sclerosisImmune cellsBrain-resident immune cellsPeripheral immune cellsPeripheral immune responseCentral nervous systemExtended major histocompatibility complexAutoimmune processControl subjectsHuman microgliaImmune responseNervous systemImmune systemHistocompatibility complexPutative susceptibility genesMicrogliaX variantGenetic architectureSusceptibility genesGenomic mapGenetic dataExpression profilesM geneSusceptibility variants
2013
Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects
Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, Noble JA, Raj T, , , Gourraud PA, Stranger BE, Oksenberg J, Olsson T, Taylor BV, Sawcer S, Hafler DA, Carrington M, De Jager PL, de Bakker PI. Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects. PLOS Genetics 2013, 9: e1003926. PMID: 24278027, PMCID: PMC3836799, DOI: 10.1371/journal.pgen.1003926.Peer-Reviewed Original ResearchMeSH KeywordsAllelesChromosome MappingGenetic Predisposition to DiseaseGenome-Wide Association StudyHaplotypesHistocompatibility Antigens Class IHLA-DP beta-ChainsHLA-DRB1 ChainsHumansIntracellular Signaling Peptides and ProteinsLinkage DisequilibriumMajor Histocompatibility ComplexMembrane ProteinsMultiple SclerosisPolymorphism, Single NucleotideReceptors, Tumor Necrosis Factor, Type IConceptsHuman leukocyte antigenNon-HLA risk allelesRisk allelesClassical human leukocyte antigenClass IMultiple sclerosis susceptibilityHLA class IIndependent effectsMS susceptibility geneMajor histocompatibility complexMajor histocompatibility complex regionHLA effectMultiple sclerosisLeukocyte antigenHLA-DRB1MS susceptibilityMultiple risk allelesDPB1 allelesClass IIPeptide-binding grooveHistocompatibility complexPolymorphic amino acid positionsTNF geneClassical allelesSusceptibility genesClinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus
Ottoboni L, Frohlich IY, Lee M, Healy BC, Keenan BT, Xia Z, Chitnis T, Guttmann CR, Khoury SJ, Weiner HL, Hafler DA, De Jager PL. Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus. Neurology 2013, 81: 1891-1899. PMID: 24174586, PMCID: PMC3843384, DOI: 10.1212/01.wnl.0000436612.66328.8a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginineChemokine CXCL10FemaleGene Expression RegulationGenetic Predisposition to DiseaseGenotypeGlutamineHEK293 CellsHumansImmunologic FactorsLongitudinal StudiesMaleMonocytesMultiple SclerosisMutationPhorbol EstersReceptors, Tumor Necrosis Factor, Type IRNA IsoformsSignal TransductionTumor Necrosis Factor-alphaConceptsTNFRSF1A locusSusceptibility allelesFunctional consequencesRobust transcriptional responseTranscriptional responseCytoplasmic domainRNA isoformsTNF-α stimulationRho GTPaseMS susceptibility genesMS geneG proteinsSusceptibility genesMolecular levelTNF pathwayGenesAltered expressionLociTNF-α pathwayAllelesRisk allelesPathwayGTPaseImmune functionTransmembrane
2009
Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor
Ban M, Goris A, Lorentzen Å, Baker A, Mihalova T, Ingram G, Booth DR, Heard RN, Stewart GJ, Bogaert E, Dubois B, Harbo HF, Celius EG, Spurkland A, Strange R, Hawkins C, Robertson NP, Dudbridge F, Wason J, De Jager PL, Hafler D, Rioux JD, Ivinson AJ, McCauley JL, Pericak-Vance M, Oksenberg JR, Hauser SL, Sexton D, Haines J, Sawcer S. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. European Journal Of Human Genetics 2009, 17: 1309-1313. PMID: 19293837, PMCID: PMC2782567, DOI: 10.1038/ejhg.2009.41.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesNon-synonymous single nucleotide polymorphismsRecent genome-wide association studiesLevel of phosphorylationAmino acid substitutionsTyrosine kinase 2 geneKinase 2 geneSingle-nucleotide polymorphism resultsSingle nucleotide polymorphismsKinase domainMultiple sclerosis susceptibility genesAssociation studiesAcid substitutionsFunctional roleSusceptibility genesNucleotide polymorphismsPolymorphism resultsTrio familiesReplication analysisGenesLociTYK2Susceptibility factorsPhosphorylationMultiple sclerosis