2015
Integrative analysis of 111 reference human epigenomes
Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller M, Amin V, Whitaker J, Schultz M, Ward L, Sarkar A, Quon G, Sandstrom R, Eaton M, Wu Y, Pfenning A, Wang X, ClaussnitzerYaping Liu M, Coarfa C, Alan Harris R, Shoresh N, Epstein C, Gjoneska E, Leung D, Xie W, David Hawkins R, Lister R, Hong C, Gascard P, Mungall A, Moore R, Chuah E, Tam A, Canfield T, Scott Hansen R, Kaul R, Sabo P, Bansal M, Carles A, Dixon J, Farh K, Feizi S, Karlic R, Kim A, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer T, Neph S, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari R, Siebenthall K, Sinnott-Armstrong N, Stevens M, Thurman R, Wu J, Zhang B, Zhou X, Abdennur N, Adli M, Akerman M, Barrera L, Antosiewicz-Bourget J, Ballinger T, Barnes M, Bates D, Bell R, Bennett D, Bianco K, Bock C, Boyle P, Brinchmann J, Caballero-Campo P, Camahort R, Carrasco-Alfonso M, Charnecki T, Chen H, Chen Z, Cheng J, Cho S, Chu A, Chung W, Cowan C, Athena Deng Q, Deshpande V, Diegel M, Ding B, Durham T, Echipare L, Edsall L, Flowers D, Genbacev-Krtolica O, Gifford C, Gillespie S, Giste E, Glass I, Gnirke A, Gormley M, Gu H, Gu J, Hafler D, Hangauer M, Hariharan M, Hatan M, Haugen E, He Y, Heimfeld S, Herlofsen S, Hou Z, Humbert R, Issner R, Jackson A, Jia H, Jiang P, Johnson A, Kadlecek T, Kamoh B, Kapidzic M, Kent J, Kim A, Kleinewietfeld M, Klugman S, Krishnan J, Kuan S, Kutyavin T, Lee A, Lee K, Li J, Li N, Li Y, Ligon K, Lin S, Lin Y, Liu J, Liu Y, Luckey C, Ma Y, Maire C, Marson A, Mattick J, Mayo M, McMaster M, Metsky H, Mikkelsen T, Miller D, Miri M, Mukame E, Nagarajan R, Neri F, Nery J, Nguyen T, O’Geen H, Paithankar S, Papayannopoulou T, Pelizzola M, Plettner P, Propson N, Raghuraman S, Raney B, Raubitschek A, Reynolds A, Richards H, Riehle K, Rinaudo P, Robinson J, Rockweiler N, Rosen E, Rynes E, Schein J, Sears R, Sejnowski T, Shafer A, Shen L, Shoemaker R, Sigaroudinia M, Slukvin I, Stehling-Sun S, Stewart R, Subramanian S, Suknuntha K, Swanson S, Tian S, Tilden H, Tsai L, Urich M, Vaughn I, Vierstra J, Vong S, Wagner U, Wang H, Wang T, Wang Y, Weiss A, Whitton H, Wildberg A, Witt H, Won K, Xie M, Xing X, Xu I, Xuan Z, Ye Z, Yen C, Yu P, Zhang X, Zhang X, Zhao J, Zhou Y, Zhu J, Zhu Y, Ziegler S, Beaudet A, Boyer L, De Jager P, Farnham P, Fisher S, Haussler D, Jones S, Li W, Marra M, McManus M, Sunyaev S, Thomson J, Tlsty T, Tsai L, Wang W, Waterland R, Zhang M, Chadwick L, Bernstein B, Costello J, Ecker J, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos J, Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. Nature 2015, 518: 317-330. PMID: 25693563, PMCID: PMC4530010, DOI: 10.1038/nature14248.Peer-Reviewed Original ResearchConceptsHuman epigenomeHuman diseasesIntegrative analysisReference human genome sequenceDiverse human traitsRoadmap Epigenomics ConsortiumHuman genome sequenceHistone modification patternsRelevant cell typesEpigenomic informationEpigenomic marksDNA accessibilityRegulatory modulesGene regulationEpigenomic studiesGenome sequenceDNA methylationGenetic variationRegulatory elementsCellular differentiationMolecular basisModification patternsEpigenomeHuman traitsCell types
2011
Genome-Wide Assessment for Genetic Variants Associated with Ventricular Dysfunction after Primary Coronary Artery Bypass Graft Surgery
Fox AA, Pretorius M, Liu KY, Collard CD, Perry TE, Shernan SK, De Jager PL, Hafler DA, Herman DS, DePalma SR, Roden DM, Muehlschlegel JD, Donahue BS, Darbar D, Seidman JG, Body SC, Seidman CE. Genome-Wide Assessment for Genetic Variants Associated with Ventricular Dysfunction after Primary Coronary Artery Bypass Graft Surgery. PLOS ONE 2011, 6: e24593. PMID: 21980348, PMCID: PMC3184087, DOI: 10.1371/journal.pone.0024593.Peer-Reviewed Original ResearchConceptsCABG surgeryPostoperative ventricular dysfunctionVentricular dysfunctionSingle nucleotide polymorphismsPrimary coronary artery bypass graft surgeryCoronary artery bypass graft surgeryArtery bypass graft surgeryPrimary CABG surgeryBypass graft surgeryClinical risk factorsMechanical ventricular supportPatient risk stratificationGenetic variantsCABG cohortGraft surgeryPostoperative morbiditySurgical patientsCardiopulmonary bypassRisk stratificationVentricular supportRisk factorsLarge cohortPrevention strategiesSurgeryMale subjectsInterferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonβ therapy in multiple sclerosis
Vosslamber S, van der Voort LF, van den Elskamp IJ, Heijmans R, Aubin C, Uitdehaag BM, Crusius JB, van der PouwKraan T, Comabella M, Montalban X, Hafler DA, De Jager PL, Killestein J, Polman CH, Verweij CL. Interferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonβ therapy in multiple sclerosis. Genes & Immunity 2011, 12: 466-472. PMID: 21471993, DOI: 10.1038/gene.2011.18.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisNon-responder statusInterferon regulatory factor 5IFNβ treatmentMultiple sclerosisT2 lesionsClinical outcomesMore magnetic resonance imagingMore T2 lesionsStart of therapyGene variantsInterferon-β TherapyIFN response genesRegulatory factor 5Poor pharmacological responseMagnetic resonance imagingIFNβ therapyClinical responseFirst relapseIndependent cohortPharmacological responseClinical relevanceG allelePatientsResonance imaging
2010
CIITA variation in the presence of HLA-DRB1*1501 increases risk for multiple sclerosis
Bronson PG, Caillier S, Ramsay PP, McCauley JL, Zuvich RL, De Jager PL, Rioux JD, Ivinson AJ, Compston A, Hafler DA, Sawcer SJ, Pericak-Vance MA, Haines JL, Consortium T, Hauser S, Oksenberg J, Barcellos L. CIITA variation in the presence of HLA-DRB1*1501 increases risk for multiple sclerosis. Human Molecular Genetics 2010, 19: 2331-2340. PMID: 20211854, PMCID: PMC2865376, DOI: 10.1093/hmg/ddq101.Peer-Reviewed Original ResearchConceptsClass II transactivator geneMultiple sclerosisPresence of HLAMHC class II transactivator geneMS risk alleleClass II MHCLogistic regression analysisG promoter variantPromoter variantsMS riskAntigen presentationII MHCIncrease riskRisk allelesMulti-stage investigationRs4774Important transcription factorSclerosisRegression analysisHLARiskStage 1Stage 2Transactivator geneAssociationGenetic 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
De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot
Greenway SC, Pereira AC, Lin JC, DePalma SR, Israel SJ, Mesquita SM, Ergul E, Conta JH, Korn JM, McCarroll SA, Gorham JM, Gabriel S, Altshuler DM, de Lourdes Quintanilla-Dieck M, Artunduaga MA, Eavey RD, Plenge RM, Shadick NA, Weinblatt ME, De Jager PL, Hafler DA, Breitbart RE, Seidman JG, Seidman CE. De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Nature Genetics 2009, 41: 931-935. PMID: 19597493, PMCID: PMC2747103, DOI: 10.1038/ng.415.Peer-Reviewed Original ResearchSoluble IL-2RA Levels in Multiple Sclerosis Subjects and the Effect of Soluble IL-2RA on Immune Responses
Maier LM, Anderson DE, Severson CA, Baecher-Allan C, Healy B, Liu DV, Wittrup KD, De Jager PL, Hafler DA. Soluble IL-2RA Levels in Multiple Sclerosis Subjects and the Effect of Soluble IL-2RA on Immune Responses. The Journal Of Immunology 2009, 182: 1541-1547. PMID: 19155502, PMCID: PMC3992946, DOI: 10.4049/jimmunol.182.3.1541.Peer-Reviewed Original ResearchConceptsMultiple sclerosisIL-2 receptorMS subjectsHealthy controlsOrgan-specific autoimmune disordersChronic systemic inflammationType 1 diabetesT cell proliferationMultiple sclerosis subjectsStrong genetic factorIL-2 signalingSIL-2RaSystemic inflammationAutoimmune disordersImmunological perturbationsAutoimmune diseasesIL-2RAControl subjectsMS casesSerum concentrationsDisease onsetSpecific allelic variantsImmune responseAggressive formDisease risk
2008
Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines
Choy E, Yelensky R, Bonakdar S, Plenge RM, Saxena R, De Jager PL, Shaw SY, Wolfish CS, Slavik JM, Cotsapas C, Rivas M, Dermitzakis ET, Cahir-McFarland E, Kieff E, Hafler D, Daly MJ, Altshuler D. Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines. PLOS Genetics 2008, 4: e1000287. PMID: 19043577, PMCID: PMC2583954, DOI: 10.1371/journal.pgen.1000287.Peer-Reviewed Original ResearchConceptsLymphoblastoid cell linesBiological noiseGenome-wide significanceInternational HapMap ProjectDrug responseCell linesGenotype-phenotype relationshipsIndividual mRNAsEQTL SNPsGenetic analysisGene expressionHapMap projectHuman cellsHuman traitsNon-genetic factorsQTLMetabolic stateModel systemGenesMRNA levelsBaseline growth ratesSpurious associationsGrowth ratePharmacogenetic experimentsEQTLsThe developing mosaic of autoimmune disease risk
Maier LM, Hafler DA. The developing mosaic of autoimmune disease risk. Nature Genetics 2008, 40: 131-132. PMID: 18227869, DOI: 10.1038/ng0208-131.Peer-Reviewed Original Research
2007
Allelic variant in CTLA4 alters T cell phosphorylation patterns
Maier LM, Anderson DE, De Jager PL, Wicker LS, Hafler DA. Allelic variant in CTLA4 alters T cell phosphorylation patterns. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 18607-18612. PMID: 18000051, PMCID: PMC2141824, DOI: 10.1073/pnas.0706409104.Peer-Reviewed Original ResearchConceptsT cell antigen receptorAllelic variationMemory T cellsAutoimmune diseasesCell antigen receptorT cell signalingT cellsFunctional effectsDisease susceptibility allelesCell signalingPhosphorylation patternPhosphorylation levelsSusceptibility variantsTCR stimulationAllelic variantsHuman immune cellsAntigen receptorGenesImmune cellsHealthy individualsCTLA4 geneCellsSpecific mAbsCTLA4Disease
2005
Multiple sclerosis
Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher‐Allan C. Multiple sclerosis. Immunological Reviews 2005, 204: 208-231. PMID: 15790361, DOI: 10.1111/j.0105-2896.2005.00240.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAutoantibodiesCentral Nervous SystemGenetic VariationHumansImmunosuppression TherapyMultiple SclerosisT-LymphocytesConceptsMultiple sclerosisT cellsB cellsImmunopathology of MSCentral nervous system white matterNervous system white matterRegulatory T cellsHallmark of inflammationImmunosuppressive therapyAutoimmune processImmunomodulatory therapeuticsAnimal modelsMS researchWhite matterDisease pathologyClonal expansionDiseaseMajor histocompatibility complex (MHC) genesMolecular pathologyRNA expressionSclerosisInflammationTherapyPathologyComplex genetic diseases
2003
Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function
Lim DG, Slavik JM, Bourcier K, Smith KJ, Hafler DA. Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function. Journal Of Experimental Medicine 2003, 198: 99-109. PMID: 12847139, PMCID: PMC2196091, DOI: 10.1084/jem.20021796.Peer-Reviewed Original ResearchConceptsT cell functionT cell clonesCell functionReactive T cell clonesCell clonesT cell responsesDifferent T cell responsesIndividual T cell clonesHLA-A2 moleculesAltered peptide ligandHLA-A2 peptideRecognition of MHCT cell receptorMHC-peptide complexesPolymorphic amino acidsFunctional outcomeHLA-A2Peptide ligandsAgonist functionMHC moleculesCell responsesEarly intracellularLong-term expressionCell receptorAntigen recognitionCTLA4 is associated with susceptibility to multiple sclerosis
Kantarci OH, Hebrink DD, Achenbach SJ, Atkinson EJ, Waliszewska A, Buckle G, McMurray CT, de Andrade M, Hafler DA, Weinshenker BG. CTLA4 is associated with susceptibility to multiple sclerosis. Journal Of Neuroimmunology 2003, 134: 133-141. PMID: 12507781, DOI: 10.1016/s0165-5728(02)00395-8.Peer-Reviewed Original ResearchAbataceptAge of OnsetAlternative SplicingAntigens, CDAntigens, DifferentiationBostonCTLA-4 AntigenDisease ProgressionDNA Mutational AnalysisExonsFemaleGenetic LinkageGenetic Predisposition to DiseaseGenetic TestingGenetic VariationGenotypeHaplotypesHumansImmunoconjugatesMaleMicrosatellite RepeatsMinnesotaMultiple SclerosisPolymorphism, Genetic