2014
Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes
Raj T, Rothamel K, Mostafavi S, Ye C, Lee MN, Replogle JM, Feng T, Lee M, Asinovski N, Frohlich I, Imboywa S, Von Korff A, Okada Y, Patsopoulos NA, Davis S, McCabe C, Paik HI, Srivastava GP, Raychaudhuri S, Hafler DA, Koller D, Regev A, Hacohen N, Mathis D, Benoist C, Stranger BE, De Jager PL. Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes. Science 2014, 344: 519-523. PMID: 24786080, PMCID: PMC4910825, DOI: 10.1126/science.1249547.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAllelesAlzheimer DiseaseAutoimmune DiseasesAutoimmunityCD4-Positive T-LymphocytesEthnicityGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunity, InnateMonocytesMultiple SclerosisNeurodegenerative DiseasesParkinson DiseasePolymorphism, Single NucleotideQuantitative Trait LociRheumatic FeverTranscriptomeConceptsSpecific immune cell typesHuman immune functionImmune cell typesMulti-ethnic cohortCell-autonomous effectsAutoimmune diseasesT cellsImmune functionParkinson's diseaseHealthy individualsInnate immunityRisk allelesDiseaseExpression quantitative trait loci (eQTL) studiesQuantitative trait loci studiesSusceptibility allelesPutative functional assignmentsCausal regulatory variantsDisease-associated lociDisease susceptibility variantsCell typesSusceptibility variantsTrans-eQTLsFunctional assignmentRegulatory variants
2013
Clinical 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
2012
Correction: The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+T Cell Proliferation
Kofler D, Severson C, Mousissian N, De Jager P, Hafler D. Correction: The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+T Cell Proliferation. The Journal Of Immunology 2012, 189: 2063-2063. DOI: 10.4049/jimmunol.1290044.Peer-Reviewed Original ResearchCell proliferationSusceptibility alleles
2011
The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+ T Cell Proliferation
Kofler DM, Severson CA, Mousissian N, De Jager PL, Hafler DA. The CD6 Multiple Sclerosis Susceptibility Allele Is Associated with Alterations in CD4+ T Cell Proliferation. The Journal Of Immunology 2011, 187: 3286-3291. PMID: 21849685, DOI: 10.4049/jimmunol.1100626.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAntigens, CDAntigens, Differentiation, T-LymphocyteCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell ProliferationCell SeparationCells, CulturedFemaleFlow CytometryGenetic Predisposition to DiseaseGenotypeHumansMaleMultiple SclerosisPhenotypeReverse Transcriptase Polymerase Chain ReactionRisk FactorsRNA, Small InterferingConceptsGenome-wide association studiesAssociation studiesAllelic variantsNew susceptibility lociSusceptibility allelesRisk allelesProliferation defectExon 5Risk-associated allelesSingle nucleotide polymorphismsExtracellular binding sitesCD6 geneSusceptibility lociLinkage disequilibriumMS risk alleleSelective knockdownT cell activationNucleotide polymorphismsAltered proliferationCell proliferationGenetic associationAllelesLong-term activationBinding sitesMS susceptibility alleles
2010
A Major Histocompatibility Class I Locus Contributes to Multiple Sclerosis Susceptibility Independently from HLA-DRB1*15:01
Cree BA, Rioux JD, McCauley JL, Gourraud PA, Goyette P, McElroy J, De Jager P, Santaniello A, Vyse TJ, Gregersen PK, Mirel D, Hafler DA, Haines JL, Pericak-Vance MA, Compston A, Sawcer SJ, Oksenberg JR, Hauser SL, , . A Major Histocompatibility Class I Locus Contributes to Multiple Sclerosis Susceptibility Independently from HLA-DRB1*15:01. PLOS ONE 2010, 5: e11296. PMID: 20593013, PMCID: PMC2892470, DOI: 10.1371/journal.pone.0011296.Peer-Reviewed Original ResearchConceptsCase-control analysisMS susceptibilityMultiple sclerosisSingle nucleotide polymorphismsClass IMS susceptibility allelesMultiple sclerosis susceptibilityMajor histocompatibility class ICochran-Armitage trend testLogistic regression modelingHLA-G geneMHC class IReplication datasetDiscovery datasetHistocompatibility class IArmitage trend testHLASignificant associationClass IIGenetic susceptibilityMajor histocompatibility complex (MHC) genesRegression modelingSusceptibility allelesP-valueMHCDissecting the Functional Consequences of the Validated Multiple Sclerosis Susceptibility Allele in TNFRSF1A
Ottoboni L, Mousissian N, Castillo I, Hafler D, De Jager P. Dissecting the Functional Consequences of the Validated Multiple Sclerosis Susceptibility Allele in TNFRSF1A. Clinical Immunology 2010, 135: s117. DOI: 10.1016/j.clim.2010.03.351.Peer-Reviewed Original ResearchSusceptibility allelesFunctional consequences
2009
Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2
Neilson DE, Adams MD, Orr CM, Schelling DK, Eiben RM, Kerr DS, Anderson J, Bassuk AG, Bye AM, Childs AM, Clarke A, Crow YJ, Di Rocco M, Dohna-Schwake C, Dueckers G, Fasano AE, Gika AD, Gionnis D, Gorman MP, Grattan-Smith PJ, Hackenberg A, Kuster A, Lentschig MG, Lopez-Laso E, Marco EJ, Mastroyianni S, Perrier J, Schmitt-Mechelke T, Servidei S, Skardoutsou A, Uldall P, van der Knaap MS, Goglin KC, Tefft DL, Aubin C, de Jager P, Hafler D, Warman ML. Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2. American Journal Of Human Genetics 2009, 84: 44-51. PMID: 19118815, PMCID: PMC2668029, DOI: 10.1016/j.ajhg.2008.12.009.Peer-Reviewed Original ResearchConceptsRecurrent ANERecurrent casesAcute Necrotizing EncephalopathyMissense mutationsCommon viral infectionsSusceptibility allelesFamilial ANENecrotizing EncephalopathyHealthy childrenViral infectionBinding protein 2PatientsAdditional kindredsAutosomal dominant traitUnaffected controlsObligate carriersIdentical mutationsProtein 2Index familySusceptibility loci