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
2020
Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
Nakatsuka N, Patterson N, Patsopoulos NA, Altemose N, Tandon A, Beecham AH, McCauley JL, Isobe N, Hauser S, De Jager PL, Hafler DA, Oksenberg JR, Reich D. Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans. Scientific Reports 2020, 10: 16902. PMID: 33037294, PMCID: PMC7547691, DOI: 10.1038/s41598-020-74035-7.Peer-Reviewed Original Research
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 variantsLatent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients
James JA, Chen H, Young KA, Bemis EA, Seifert J, Bourn RL, Deane KD, Demoruelle MK, Feser M, O'Dell JR, Weisman MH, Keating RM, Gaffney PM, Kelly JA, Langefeld CD, Harley JB, Robinson W, Hafler DA, O'Connor KC, Buckner J, Guthridge JM, Norris JM, Holers VM. Latent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients. EBioMedicine 2019, 42: 76-85. PMID: 30952617, PMCID: PMC6491794, DOI: 10.1016/j.ebiom.2019.03.063.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusFirst-degree relativesGenetic risk scoreRA patientsRheumatoid arthritisSLE patientsT1D patientsAutoantibody-positive systemic lupus erythematosusRisk first-degree relativesOrgan-specific autoimmune diseasesType 1 diabetes patientsAutoimmune disease preventionAnti-tissue transglutaminaseDisease-associated autoantibodiesDisease prevention studiesUnaffected first-degree relativesCross-sectional studyLatent autoimmunityLupus erythematosusAutoimmune diseasesDiabetes patientsPrevention StudyRisk scoreAutoimmunityPreclinical period
2018
Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis
Ponath G, Lincoln MR, Levine-Ritterman M, Park C, Dahlawi S, Mubarak M, Sumida T, Airas L, Zhang S, Isitan C, Nguyen TD, Raine CS, Hafler DA, Pitt D. Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis. Nature Communications 2018, 9: 5337. PMID: 30559390, PMCID: PMC6297228, DOI: 10.1038/s41467-018-07785-8.Peer-Reviewed Original ResearchMeSH KeywordsAstrocytesCells, CulturedCentral Nervous SystemGenetic Predisposition to DiseaseHumansMultiple SclerosisNF-kappa B p50 SubunitPolymorphism, Single NucleotideRisk FactorsTranscription Factor RelAConceptsMultiple sclerosisAstrocyte responseRisk variantsLocal autoimmune inflammationPeripheral immune cellsCentral nervous system cellsPeripheral immune systemCultured human astrocytesNervous system cellsNF-κB signalingCNS accessDysfunctional lymphocytesAstroglial functionAutoimmune inflammationLymphocytic infiltrateLymphocyte recruitmentImmune cellsGenetic risk allelesGenetic risk variantsMS lesionsMS susceptibilityHuman astrocytesLesion sizeImmune systemSystem cells
2016
NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk
Consortium T, Antel J, Ban M, Baranzini S, Barcellos L, Barizzone N, Beecham A, Berge T, Bernardinelli L, Booth D, Bos S, Buck D, Butkiewicz M, Celius E, Comabella M, Compston A, Dedham K, Cotsapas C, Alfonso S, De Jager P, Dubois B, Duquette P, Fontaine B, Gasperi C, Gil E, Goris A, Gourraud P, Graetz C, Gyllenberg A, Hadjigeorgiou G, Hafler D, Hribko D, Haines J, Harbo H, Hauser S, Warto S, Hawkins C, Hemmer B, Henry R, Hintzen R, Horakova D, Ivinson A, Howard M, Jelcic I, Kaskow B, Kira J, Kleinova P, Kockum I, Kucerova K, Lill C, Luessi F, Malhotra S, Martin R, Martinelli F, Matsushita T, McCabe C, McCauley J, Mescheriakkova J, Mitrovic M, Moen S, Montalban X, Muhlau M, Nakmura Y, Oksenberg J, Olsson T, Oturai A, Palotie A, Patsopoulos N, Pavlicova J, Pericak-Vance P, Piehl F, Rebeix I, Rioux J, Saarela J, Sawcer S, Sellebjerg F, Sondergaard H, Sorensen P, Sospedra M, Spurkland A, Stewart G, Taylor B, Uitterlinden A, Van Duijn C, Zipp F. NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk. Neuron 2016, 92: 333-335. PMID: 27764667, PMCID: PMC5641967, DOI: 10.1016/j.neuron.2016.09.052.Peer-Reviewed Original ResearchConceptsPrimary progressive diseaseMultiple sclerosis riskProgressive diseaseMultiple sclerosisPatient's likelihoodDisease subtypesPatient collectionInsufficient sample sizeCommon variant associationsLow-frequency associationMendelian formsAssociationRecent studiesCertain individualsSample sizeVariant associationsSclerosisSubtypesDiseaseNeuronsThe Link Between CD6 and Autoimmunity: Genetic and Cellular Associations.
Kofler DM, Farkas A, von Bergwelt-Baildon M, Hafler DA. The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations. Current Drug Targets 2016, 17: 651-65. PMID: 26844569, DOI: 10.2174/1389450117666160201105934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteArthritis, RheumatoidAutoimmunityCD4-Positive T-LymphocytesCell Adhesion Molecules, NeuronalClinical Trials as TopicDisease Models, AnimalFetal ProteinsGenetic Predisposition to DiseaseHumansMultiple SclerosisPolymorphism, Single NucleotideConceptsMultiple sclerosisRheumatoid arthritisCentral nervous systemNervous systemSingle nucleotide polymorphismsDevelopment of MSTreatment of RARole of CD6T cell traffickingT cell functionGenetic risk factorsEndothelial cell barrierCD6 geneClinical responseGenetic associationClinical featuresAutoimmune diseasesSynovial cellsRisk factorsTumor necrosisSynovial fibroblastsPossible common mechanismT cellsT lymphocytesLeukocyte trafficking
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
2014
Monoallelic expression of the human FOXP2 speech gene
Adegbola AA, Cox GF, Bradshaw EM, Hafler DA, Gimelbrant A, Chess A. Monoallelic expression of the human FOXP2 speech gene. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 112: 6848-6854. PMID: 25422445, PMCID: PMC4460484, DOI: 10.1073/pnas.1411270111.Peer-Reviewed Original ResearchMeSH KeywordsApraxiasComparative Genomic HybridizationFemaleForkhead Transcription FactorsGene Expression ProfilingGene Expression Regulation, DevelopmentalGenes, X-LinkedHumansPolymorphism, Single NucleotideReverse Transcriptase Polymerase Chain ReactionSequence Analysis, DNASequence DeletionSpeechX Chromosome InactivationConceptsRandom monoallelic expressionMonoallelic expressionAllele-specific expressionNumber of genesHuman Mendelian disordersForkhead box P2 (FOXP2) geneP2 geneAutosomal genesMore genesAutosomal genomeX chromosomeGene expressionHaploinsufficiency phenotypeMendelian disordersGenesDevelopmental verbal dyspraxiaFOXP2 mutationsIntriguing possibilityFOXP2 geneExpressionRecent descriptionMutationsVerbal dyspraxiaAutosomesGenomeGenetic and epigenetic fine mapping of causal autoimmune disease variants
Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Whitton H, Ryan RJ, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Hafler DA, Bernstein BE. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 2014, 518: 337-343. PMID: 25363779, PMCID: PMC4336207, DOI: 10.1038/nature13835.Peer-Reviewed Original ResearchConceptsCausal variantsAutoimmune diseasesT cellsRegulatory T cellsNon-coding risk variantsT cell subsetsEnhancer-associated RNAsGenome-wide association studiesPrimary immune cellsCandidate causal variantsGene regulatory modelsImmune cellsImmune stimulationB cellsGene activationFine mappingTranscription factorsMaster regulatorHistone acetylationImmune differentiationSequence determinantsGene expressionAssociation studiesDiseaseHuman diseasesPolarization 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 variantsCommon Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells
Lee MN, Ye C, Villani AC, Raj T, Li W, Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K, Ward LD, Raddassi K, McCabe C, Lee MH, Frohlich IY, Hafler DA, Kellis M, Raychaudhuri S, Zhang F, Stranger BE, Benoist CO, De Jager PL, Regev A, Hacohen N. Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells. Science 2014, 343: 1246980. PMID: 24604203, PMCID: PMC4124741, DOI: 10.1126/science.1246980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoimmune DiseasesCommunicable DiseasesDendritic CellsEscherichia coliFemaleGene-Environment InteractionGenetic LociGenome-Wide Association StudyHEK293 CellsHost-Pathogen InteractionsHumansInfluenza A virusInterferon Regulatory Factor-7Interferon-betaLipopolysaccharidesMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociSTAT Transcription FactorsTranscriptomeYoung AdultConceptsGenetic variationPathogen-responsive genesHuman genetic variationGenetic variantsIRF transcription factorsCommon genetic variantsType I IFN inductionFunctional annotationExpression responsesTranscription factorsI IFN inductionCausal variantsPathogen sensingEnvironmental stimuliComplex diseasesCommon variantsCommon allelesIFN inductionComputational approachVariantsCellsInductionGenesInterindividual variationSTAT
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 genesNetwork-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 approach
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 consequencesGenome-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 subjectsPervasive Sharing of Genetic Effects in Autoimmune Disease
Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, Wallace C, Abecasis GR, Barrett JC, Behrens T, Cho J, De Jager PL, Elder JT, Graham RR, Gregersen P, Klareskog L, Siminovitch KA, van Heel DA, Wijmenga C, Worthington J, Todd JA, Hafler DA, Rich SS, Daly MJ, . Pervasive Sharing of Genetic Effects in Autoimmune Disease. PLOS Genetics 2011, 7: e1002254. PMID: 21852963, PMCID: PMC3154137, DOI: 10.1371/journal.pgen.1002254.Peer-Reviewed Original ResearchMeSH KeywordsAutoimmune DiseasesCluster AnalysisComorbidityGenetic LociGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideProtein Interaction MapsConceptsSingle nucleotide polymorphismsSystemic lupus erythematosusImmune-mediated diseasesType 1 diabetesGenetic risk factorsMajor histocompatibility locusCommon autoimmuneCommon single nucleotide polymorphismsLupus erythematosusCrohn's diseaseRheumatoid arthritisClinical evidenceMultiple sclerosisAutoimmune diseasesRisk single nucleotide polymorphismsCeliac diseaseInflammatory diseasesRisk factorsMeta-AnalysisDisease riskDiseaseHistocompatibility locusUnderlying mechanismGenetic associationNucleotide polymorphismsInterferon 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 imagingA 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 ResearchMeSH KeywordsCalciumCytoskeletonDisease SusceptibilityEpistasis, GeneticGenetic LociGenome-Wide Association StudyHumansMultiple SclerosisPolymorphism, Single NucleotideSignal TransductionConceptsGenome-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
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 investigation