2015
Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli
Housley WJ, Fernandez SD, Vera K, Murikinati SR, Grutzendler J, Cuerdon N, Glick L, De Jager PL, Mitrovic M, Cotsapas C, Hafler DA. Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli. Science Translational Medicine 2015, 7: 291ra93. PMID: 26062845, PMCID: PMC4574294, DOI: 10.1126/scitranslmed.aaa9223.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAllelesAutoimmunityCase-Control StudiesCD4-Positive T-LymphocytesCell NucleusCytokinesFemaleGenetic Predisposition to DiseaseHumansInflammationMaleMiddle AgedMultiple SclerosisNF-kappa BPolymorphism, Single NucleotideProtein TransportReceptors, Tumor Necrosis Factor, Type IRisk FactorsSex CharacteristicsSignal TransductionTime FactorsTumor Necrosis Factor-alphaConceptsB-cell leukemia 3Multiple sclerosisNegative regulatorInflammatory stimuliGenetic variantsWide association studyDisease susceptibility variantsNaïve CD4 T cellsRapid genetic screeningCD4 T cellsActivation of p65Transcription factor nuclear factor κBExpression of NFκBNuclear factor κBApoptosis 1Cellular inhibitorGG risk genotypeDegradation of inhibitorCentral regulatorAssociation studiesCytokine blockadeUlcerative colitisAutoimmune diseasesTumor necrosisSusceptibility 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
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci
De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, Piccio L, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S, Baranzini S, McCauley J, Pericak-Vance M, Haines J, Gibson R, Naeglin Y, Uitdehaag B, Matthews P, Kappos L, Polman C, McArdle W, Strachan D, Evans D, Cross A, Daly M, Compston A, Sawcer S, Weiner H, Hauser S, Hafler D, Oksenberg J. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nature Genetics 2009, 41: 776-782. PMID: 19525953, PMCID: PMC2757648, DOI: 10.1038/ng.401.Peer-Reviewed Original Research