2014
Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cells
2011
Genome‐wide meta‐analysis identifies novel multiple sclerosis susceptibility loci
Patsopoulos NA, Esposito F, Reischl J, Lehr S, Bauer D, Heubach J, Sandbrink R, Pohl C, Edan G, Kappos L, Miller D, Montalbán J, Polman C, Freedman M, Hartung H, Arnason B, Comi G, Cook S, Filippi M, Goodin D, Jeffery D, O'Connor P, Ebers G, Langdon D, Reder A, Traboulsee A, Zipp F, Schimrigk S, Hillert J, Bahlo M, Booth D, Broadley S, Brown M, Browning B, Browning S, Butzkueven H, Carroll W, Chapman C, Foote S, Griffiths L, Kermode A, Kilpatrick T, Lechner-Scott J, Marriott M, Mason D, Moscato P, Heard R, Pender M, Perreau V, Perera D, Rubio J, Scott R, Slee M, Stankovich J, Stewart G, Taylor B, Tubridy N, Willoughby E, Wiley J, Matthews P, Boneschi F, Compston A, Haines J, Hauser S, McCauley J, Ivinson A, Oksenberg J, Pericak-Vance M, Sawcer S, De Jager P, Hafler D, de Bakker P. Genome‐wide meta‐analysis identifies novel multiple sclerosis susceptibility loci. Annals Of Neurology 2011, 70: 897-912. PMID: 22190364, PMCID: PMC3247076, DOI: 10.1002/ana.22609.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle nucleotide polymorphismsSusceptibility lociHapMap Phase IIUnique single nucleotide polymorphismsGene discovery effortsNew susceptibility lociStrongest cis effectsMS genome-wide association studiesQuantitative trait analysisFlanking genesGenetic architectureRNA expression dataMultiple sclerosis susceptibility lociIntergenic regionSecond intronNew lociNovel susceptibility allelesAdditional lociTrait analysisAssociation studiesExpression dataChromosome 2p21LociFunctional consequencesA knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility
Bush WS, McCauley JL, DeJager PL, Dudek SM, Hafler DA, Gibson RA, Matthews PM, Kappos L, Naegelin Y, Polman CH, Hauser SL, Oksenberg J, Haines JL, Ritchie MD. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility. Genes & Immunity 2011, 12: 335-340. PMID: 21346779, PMCID: PMC3136581, DOI: 10.1038/gene.2011.3.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGene-gene interactionsCytoskeleton regulatory proteinsCytoskeletal regulationGenetic architectureGene clusterInteraction analysisSingle-locus analysisGWAS dataRegulatory proteinsBiological contextRelated genesAssociation studiesSusceptibility lociWeak main effectsPhospholipase CGenetic effectsΒ isoformsComplex diseasesBiological mechanismsNeurodegenerative mechanismsNew genetic effectsEpistasisACTN1Genes
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 replicationScreenIL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production
Maier LM, Lowe CE, Cooper J, Downes K, Anderson DE, Severson C, Clark PM, Healy B, Walker N, Aubin C, Oksenberg JR, Hauser SL, Compston A, Sawcer S, , De Jager PL, Wicker LS, Todd JA, Hafler DA. IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production. PLOS Genetics 2009, 5: e1000322. PMID: 19119414, PMCID: PMC2602853, DOI: 10.1371/journal.pgen.1000322.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT1D subjectsSoluble interleukin-2 receptor productionSoluble interleukin-2 receptorOrgan-specific autoimmune disordersHealthy control subjectsInterleukin-2 receptorType 1 diabetesHuman leukocyte antigen (HLA) complexMS risk genesAutoimmune disordersControl subjectsAutoimmunity riskHealthy controlsIL2RA regionType 1Autoimmune lociRisk allelesReceptor productionCandidate gene association studiesAntigen complexGene association studiesAssociation studiesT1D.Sclerosis
1994
T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice.
Kuchroo VK, Collins M, al-Sabbagh A, Sobel RA, Whitters MJ, Zamvil SS, Dorf ME, Hafler DA, Seidman JG, Weiner HL. T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice. Journal Of Experimental Medicine 1994, 179: 1659-1664. PMID: 8163944, PMCID: PMC2191471, DOI: 10.1084/jem.179.5.1659.Peer-Reviewed Original ResearchConceptsExperimental allergic encephalomyelitisMyelin basic proteinAutoimmune diseasesEncephalitogenic epitopeTCR repertoireTCR VProteolipid proteinTransgenic miceT cell receptor usageDiverse T cell repertoireT cell receptor repertoireExperimental autoimmune encephalomyelitisAutoreactive T cellsCell receptor repertoireT cell repertoireT cell clonesAutoimmune encephalomyelitisAllergic encephalomyelitisSJL miceT cellsCell repertoirePLP epitopesReceptor usageReceptor repertoireImmunization