2024
Genetic mapping across autoimmune diseases reveals shared associations and mechanisms
Lincoln M, Connally N, Axisa P, Gasperi C, Mitrovic M, van Heel D, Wijmenga C, Withoff S, Jonkers I, Padyukov L, Rich S, Graham R, Gaffney P, Langefeld C, Vyse T, Hafler D, Chun S, Sunyaev S, Cotsapas C. Genetic mapping across autoimmune diseases reveals shared associations and mechanisms. Nature Genetics 2024, 56: 838-845. PMID: 38741015, DOI: 10.1038/s41588-024-01732-8.Peer-Reviewed Original ResearchConceptsGenetic mapResolution of genetic mappingExpression quantitative trait lociFine-mapping resolutionQuantitative trait lociGenomic lociTrait lociPolygenic disorderAllelesRisk allelesLociPathogenic mechanismsImmune systemAutoimmune mechanismsAutoimmune diseasesInflammatory diseasesTraitsMechanismDiseaseSample collectionExpression
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
2016
Evaluation of KIR4.1 as an Immune Target in Multiple Sclerosis
Chastre A, Hafler DA, O'Connor KC. Evaluation of KIR4.1 as an Immune Target in Multiple Sclerosis. New England Journal Of Medicine 2016, 374: 1495-1496. PMID: 27074083, PMCID: PMC4918464, DOI: 10.1056/nejmc1513302.Peer-Reviewed Original Research
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 variantsFunctional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Science Translational Medicine 2015, 7: 287ra74. PMID: 25972006, PMCID: PMC4497538, DOI: 10.1126/scitranslmed.aaa8038.Peer-Reviewed Original ResearchMeSH KeywordsAdultCase-Control StudiesFemaleGene Expression ProfilingHumansInflammationMaleMiddle AgedMultiple SclerosisMyelin SheathT-LymphocytesConceptsMyelin-reactive T cellsMultiple sclerosisT cellsHealthy controlsT cell librariesT helper cell 17Antigen-specific T cellsGene signatureMore IL-10More proinflammatory cytokinesAutoreactive T cellsIL-10 productionHuman autoimmune diseasesGranulocyte-macrophage colony-stimulating factorProduction of interferonColony-stimulating factorMyelin antigensTh17 cellsIL-10Inflammatory profileInterleukin-17Proinflammatory cytokinesAutoimmune diseasesDisease progressionHealthy subjects
2014
Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells
Kofler DM, Marson A, Dominguez-Villar M, Xiao S, Kuchroo VK, Hafler DA. Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells. Journal Of Clinical Investigation 2014, 124: 2513-2522. PMID: 24812667, PMCID: PMC4089462, DOI: 10.1172/jci72973.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAutoimmunityCase-Control StudiesDinoprostoneDown-RegulationFemaleGene Knockdown TechniquesGene SilencingHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedModels, ImmunologicalMultiple SclerosisNuclear Receptor Subfamily 1, Group F, Member 3PhenotypePromoter Regions, GeneticReceptors, Prostaglandin E, EP2 SubtypeSignal TransductionTh17 CellsConceptsTh17 cell phenotypeProstaglandin receptor EP2Receptor EP2Healthy individualsOverexpression of EP2Transcription factor RORCT cell subsetsEffects of PGE2Cell phenotypeExpression of IFNInflammatory gene transcriptionPGE2-dependent pathwayTh17 cellsWT miceAutoimmune diseasesCell subsetsHealthy subjectsEP2 expressionGM-CSFEP2RORCCD4Cell typesCellsGene transcription
2013
Network-Based Multiple Sclerosis Pathway Analysis with GWAS Data from 15,000 Cases and 30,000 Controls
Consortium I, Baranzini S, Khankhanian P, Patsopoulos N, Li M, Stankovich J, Cotsapas C, Søndergaard H, Ban M, Barizzone N, Bergamaschi L, Booth D, Buck D, Cavalla P, Celius E, Comabella M, Comi G, Compston A, Cournu-Rebeix I, D’alfonso S, Damotte V, Din L, Dubois B, Elovaara I, Esposito F, Fontaine B, Franke A, Goris A, Gourraud P, Graetz C, Guerini F, Guillot-Noel L, Hafler D, Hakonarson H, Hall P, Hamsten A, Harbo H, Hemmer B, Hillert J, Kemppinen A, Kockum I, Koivisto K, Larsson M, Lathrop M, Leone M, Lill C, Macciardi F, Martin R, Martinelli V, Martinelli-Boneschi F, McCauley J, Myhr K, Naldi P, Olsson T, Oturai A, Pericak-Vance M, Perla F, Reunanen M, Saarela J, Saker-Delye S, Salvetti M, Sellebjerg F, Sørensen P, Spurkland A, Stewart G, Taylor B, Tienari P, Winkelmann J, Consortium W, Zipp F, Ivinson A, Haines J, Sawcer S, DeJager P, Hauser S, Oksenberg J. Network-Based Multiple Sclerosis Pathway Analysis with GWAS Data from 15,000 Cases and 30,000 Controls. American Journal Of Human Genetics 2013, 92: 854-865. PMID: 23731539, PMCID: PMC3958952, DOI: 10.1016/j.ajhg.2013.04.019.Peer-Reviewed Original ResearchConceptsPathway analysisNetwork-based pathway analysisGenome-wide association studiesSubnetworks of genesExtended linkage disequilibriumNon-HLA susceptibility lociHigh-confidence candidatesSubsequent genetic studiesComplex traitsSubstantial genetic componentSignificant lociGWAS dataAssociation studiesGene levelGenetic studiesNominal statistical evidenceSusceptibility lociGenesLinkage disequilibriumSusceptibility variantsGenetic componentRelated pathwaysLociHuman leukocyte antigen (HLA) regionPowerful approachSpecific peripheral B cell tolerance defects in patients with multiple sclerosis
Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P, Herold KC, Hafler DA, O’Connor K, Meffre E. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. Journal Of Clinical Investigation 2013, 123: 2737-2741. PMID: 23676463, PMCID: PMC3668812, DOI: 10.1172/jci68775.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAutoantigensB-LymphocytesCase-Control StudiesFlow CytometryHumansMultiple SclerosisPeripheral ToleranceT-Lymphocytes, RegulatoryConceptsB cell tolerance checkpointsB cell tolerance defectsMultiple sclerosisRheumatoid arthritisTolerance checkpointsB cellsPeripheral B cell tolerance checkpointsTolerance defectsAutoreactive B cell clonesMature naive B cellsType 1 diabetesAutoreactive B cellsB cell toleranceCentral nervous systemNaive B cellsB cell clonesB cell selectionEarly B cell developmentIPEX patientsMost patientsTreg functionHomeostatic proliferationAutoimmune diseasesPatientsHealthy individualsPhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis
Larman HB, Laserson U, Querol L, Verhaeghen K, Solimini NL, Xu GJ, Klarenbeek PL, Church GM, Hafler DA, Plenge RM, Nigrovic PA, De Jager PL, Weets I, Martens GA, O'Connor KC, Elledge SJ. PhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis. Journal Of Autoimmunity 2013, 43: 1-9. PMID: 23497938, PMCID: PMC3677742, DOI: 10.1016/j.jaut.2013.01.013.Peer-Reviewed Original ResearchConceptsType 1 diabetes patientsRheumatoid arthritis patientsMultiple sclerosis patientsLoss of tolerancePhage immunoprecipitation sequencingType 1 diabetesNeurological autoimmunitySeropositivity statusArthritis patientsRheumatoid arthritisSclerosis patientsMultiple sclerosisAutoimmune diseasesDiabetes patientsCerebrospinal fluidGeneral populationSynovial fluidHealthy seraPatientsSusceptible individualsAntibody specificityDiseaseReceptor specificitySerumHuman peptidome
2012
Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes
Costantino CM, Spooner E, Ploegh HL, Hafler DA. Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes. PLOS ONE 2012, 7: e29805. PMID: 22299025, PMCID: PMC3267721, DOI: 10.1371/journal.pone.0029805.Peer-Reviewed Original ResearchMeSH KeywordsAntigen PresentationAntigen-Antibody ComplexAutoantigensBlood DonorsB-LymphocytesCase-Control StudiesCD4-Positive T-LymphocytesCell Line, TransformedHistocompatibility Antigens Class IIHLA-DR AntigensHumansModels, BiologicalPeptidesProteomeSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationTandem Mass SpectrometryT-LymphocytesConceptsHLA-DRT cellsPeptide repertoireSelf-antigen presentationAntigen presenting cellsEndogenous peptide repertoireB cell repertoireT-cell processMHC-peptide complexesIL-2Presenting cellsAPC typesT lymphocytesCell repertoireNovel epitopesB cellsHuman BEndogenous epitopesClass II MHC-peptide complexesPeptide epitopesEpitopesCellsCell processesCell-specific proteomesVast majority
2010
Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals
Briggs FB, Bartlett SE, Goldstein BA, Wang J, McCauley JL, Zuvich RL, De Jager PL, Rioux JD, Ivinson AJ, Compston A, Hafler DA, Hauser SL, Oksenberg JR, Sawcer SJ, Pericak-Vance MA, Haines JL, Consortium I, Barcellos L. Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals. Human Molecular Genetics 2010, 19: 4286-4295. PMID: 20699326, PMCID: PMC2951862, DOI: 10.1093/hmg/ddq328.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesHumansMass SpectrometryMultiple SclerosisPolymorphism, Single NucleotideReceptors, Corticotropin-Releasing HormoneConceptsMultiple sclerosisMS casesHealthy controlsCRHR1 variantsCorticotrophin-releasing hormone receptor 1Primary genetic risk factorAdrenal (HPA) axis genesHPA axis regulationGenetic risk factorsHormone receptor 1European ancestryMS pathogenesisSystem involvementRisk factorsUnivariate analysisAxis regulationReceptor 1Axis genesStrong associationCRHR1Lines of evidenceSclerosisDiscovery datasetImportant predictorFurther investigationA 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-valueMHCA non-synonymous SNP within membrane metalloendopeptidase-like 1 (MMEL1) is associated with multiple sclerosis
Ban M, McCauley JL, Zuvich R, Baker A, Bergamaschi L, Cox M, Kemppinen A, D'Alfonso S, Guerini FR, Lechner-Scott J, Dudbridge F, Wason J, Robertson NP, De Jager PL, Hafler DA, Barcellos LF, Ivinson AJ, Sexton D, Oksenberg JR, Hauser SL, Pericak-Vance MA, Haines J, Compston A, Sawcer S. A non-synonymous SNP within membrane metalloendopeptidase-like 1 (MMEL1) is associated with multiple sclerosis. Genes & Immunity 2010, 11: 660-664. PMID: 20574445, PMCID: PMC2946966, DOI: 10.1038/gene.2010.36.Peer-Reviewed Original ResearchFunctionally defective germline variants of sialic acid acetylesterase in autoimmunity
Surolia I, Pirnie SP, Chellappa V, Taylor KN, Cariappa A, Moya J, Liu H, Bell DW, Driscoll DR, Diederichs S, Haider K, Netravali I, Le S, Elia R, Dow E, Lee A, Freudenberg J, De Jager PL, Chretien Y, Varki A, MacDonald ME, Gillis T, Behrens TW, Bloch D, Collier D, Korzenik J, Podolsky DK, Hafler D, Murali M, Sands B, Stone JH, Gregersen PK, Pillai S. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 2010, 466: 243-247. PMID: 20555325, PMCID: PMC2900412, DOI: 10.1038/nature09115.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAcetylesteraseAllelesAnimalsAntibodies, AntinuclearArthritis, RheumatoidAutoimmune DiseasesAutoimmunityBiocatalysisB-LymphocytesCarboxylic Ester HydrolasesCase-Control StudiesCell LineDiabetes Mellitus, Type 1EuropeExonsGenetic Predisposition to DiseaseGerm-Line MutationHumansMiceN-Acetylneuraminic AcidOdds RatioPolymorphism, Single NucleotideSample SizeSequence Analysis, DNAGenome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene
Jakkula E, Leppä V, Sulonen AM, Varilo T, Kallio S, Kemppinen A, Purcell S, Koivisto K, Tienari P, Sumelahti ML, Elovaara I, Pirttilä T, Reunanen M, Aromaa A, Oturai AB, Søndergaard HB, Harbo HF, Mero IL, Gabriel SB, Mirel DB, Hauser SL, Kappos L, Polman C, De Jager PL, Hafler DA, Daly MJ, Palotie A, Saarela J, Peltonen L. Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene. American Journal Of Human Genetics 2010, 86: 285-291. PMID: 20159113, PMCID: PMC2820168, DOI: 10.1016/j.ajhg.2010.01.017.Peer-Reviewed Original ResearchConceptsSTAT3 geneGenome-wide association studiesRare risk allelesComplex traitsRisk lociRisk allelesAssociated variantsAssociation studiesRecent GWASInternal isolateLociCommon variantsGenetic riskGenesAllelesCritical roleSTAT3Small odds ratiosHeterogeneous populationVariantsGWASIsolatesProtective haplotypeTraitsSNPsGenetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility
Zuvich RL, McCauley JL, Oksenberg JR, Sawcer SJ, De Jager PL, International Multiple Sclerosis Genetics Consortium, Aubin C, Cross AH, Piccio L, Aggarwal NT, Evans D, Hafler DA, Compston A, Hauser SL, Pericak-Vance MA, Haines JL. Genetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility. Human Genetics 2010, 127: 525-535. PMID: 20112030, PMCID: PMC2854871, DOI: 10.1007/s00439-010-0789-4.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsGene regionCase-control data setsPutative functional relationshipsNovel gene regionsIndependent case-control data setDense SNP mapReceptor alpha-chain geneIllumina Infinium BeadChipExperiment-wise significanceNovel associationsAlpha chain geneGenetic architectureComplex traitsStrong genetic componentGenetic variationSNP mapInfinium BeadChipAffordable genotypingBiological pathwaysGenesGenetic componentChain geneTYK2 geneNumerous family studies
2009
Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci
, , McCauley J, Zuvich R, Beecham A, De Jager P, Konidari I, Whitehead P, Aubin C, Ban M, Pobywajlo S, Briskin R, Romano S, Aggarwal N, Piccio L, McArdle W, Strachan D, Evans D, Cross A, Cree B, Rioux J, Barcellos L, Ivinson A, Compston A, Hafler D, Hauser S, Oksenberg J, Sawcer S, Pericak-Vance M, Haines J. Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci. Human Molecular Genetics 2009, 19: 953-962. PMID: 20007504, PMCID: PMC2816610, DOI: 10.1093/hmg/ddp542.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle nucleotide polymorphismsAssociation studiesFirst genome-wide association studyGenome-wide association screenNumerous complex diseasesSusceptibility lociInitial genome-wide association studyGenome-wide significanceNovel susceptibility lociComplex genetic diseasesHundreds of associationsSNP hitsGWAS studiesGenetic diseasesLociComplex diseasesOriginal screenTMEM39AInitial associationIndependent data setsReplicationKIF21BInitial replicationScreenMeta-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 ResearchThe role of the CD58 locus in multiple sclerosis
De Jager PL, Baecher-Allan C, Maier LM, Arthur AT, Ottoboni L, Barcellos L, McCauley JL, Sawcer S, Goris A, Saarela J, Yelensky R, Price A, Leppa V, Patterson N, de Bakker PI, Tran D, Aubin C, Pobywajlo S, Rossin E, Hu X, Ashley CW, Choy E, Rioux JD, Pericak-Vance MA, Ivinson A, Booth DR, Stewart GJ, Palotie A, Peltonen L, Dubois B, Haines JL, Weiner HL, Compston A, Hauser SL, Daly MJ, Reich D, Oksenberg JR, Hafler DA. The role of the CD58 locus in multiple sclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 5264-5269. PMID: 19237575, PMCID: PMC2664005, DOI: 10.1073/pnas.0813310106.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMS subjectsMononuclear cellsCD58 expressionProtective effectMRNA expressionPeripheral blood mononuclear cellsRegulatory T cellsBlood mononuclear cellsTranscription factor Foxp3Dose-dependent increaseCentral nervous systemLymphoblastic cell linesClinical remissionAxonal lossControl subjectsInflammatory diseasesFactor Foxp3T cellsWhole-genome association scansLFA-3Nervous systemProtective allelesPotential mechanismsSclerosisUse of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS
Kallio SP, Jakkula E, Purcell S, Suvela M, Koivisto K, Tienari PJ, Elovaara I, Pirttilä T, Reunanen M, Bronnikov D, Viander M, Meri S, Hillert J, Lundmark F, Harbo HF, Lorentzen Å, De Jager PL, Daly MJ, Hafler DA, Palotie A, Peltonen L, Saarela J. Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS. Human Molecular Genetics 2009, 18: 1670-1683. PMID: 19221116, PMCID: PMC2667286, DOI: 10.1093/hmg/ddp073.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesChromosomes, Human, Pair 5Complement C7FinlandGenome-Wide Association StudyHaplotypesHumansMultiple Sclerosis