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The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

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dc.creatorKottyan, Leah C.spa
dc.creatorZoller, Erin E.spa
dc.creatorBene, Jessicaspa
dc.creatorLu, Xiaomingspa
dc.creatorKelly, Jennifer A.spa
dc.creatorRupert, Andrew M.spa
dc.creatorLessard, Christopher J.spa
dc.creatorVaughn, Samuel E.spa
dc.creatorMarion, Mirandaspa
dc.creatorWeirauch, Matthew T.spa
dc.creatorNamjou, Bahramspa
dc.creatorAdler, Adamspa
dc.creatorRasmussen, Astridspa
dc.creatorGlenn, Stuartspa
dc.creatorMontgomery, Courtney G.spa
dc.creatorHirschfield, Gideon M.spa
dc.creatorXie, Gangspa
dc.creatorColtescu, Catalinaspa
dc.creatorAmos, Chrisspa
dc.creatorLi, Hespa
dc.creatorIce, John A.spa
dc.creatorNath, Swapan K.spa
dc.creatorMariette, Xavierspa
dc.creatorBowman, Simonspa
dc.creatorRischmueller, Maureenspa
dc.creatorLester, Suespa
dc.creatorBrun, Johan G.spa
dc.creatorGøransson, Lasse G.spa
dc.creatorHarboe, Ernaspa
dc.creatorOmdal, Roaldspa
dc.creatorCunninghame-Graham, Deborah S.spa
dc.creatorVyse, Timspa
dc.creatorMiceli-Richard, Corinnespa
dc.creatorBrennan, Michael T.spa
dc.creatorLessard, James A.spa
dc.creatorWahren-Herlenius, Mariespa
dc.creatorKvarnström, Marikaspa
dc.creatorIllei, Gabor G.spa
dc.creatorWitte, Torstenspa
dc.creatorJonsson, Rolandspa
dc.creatorEriksson, Perspa
dc.creatorNordmark, Gunnelspa
dc.creatorNg, Wan-Faispa
dc.creatorAnaya, Juan-Manuelspa
dc.creatorRhodus, Nelson L.spa
dc.creatorSegal, Barbara M.spa
dc.creatorMerrill, Joan T.spa
dc.creatorJames, Judith A.spa
dc.creatorGuthridge, Joel M.spa
dc.creatorScofield, R. Halspa
dc.creatorAlarcon-Riquelme, Martaspa
dc.creatorBae, Sang-Cheolspa
dc.creatorBoackle, Susan A.spa
dc.creatorCriswell, Lindsey A.spa
dc.creatorGilkeson, Garyspa
dc.creatorKamen, Diane L.spa
dc.creatorJacob, Chaim O.spa
dc.creatorKimberly, Robertspa
dc.creatorBrown, Elizabethspa
dc.creatorEdberg, Jeffreyspa
dc.creatorAlarcón, Graciela S.spa
dc.creatorReveille, John D.spa
dc.creatorVilá, Luis M.spa
dc.creatorPetri, Michellespa
dc.creatorRamsey-Goldman, Rosalindspa
dc.creatorFreedman, Barry I.spa
dc.creatorNiewold, Timothyspa
dc.creatorStevens, Anne M.spa
dc.creatorTsao, Betty P.spa
dc.creatorYing, Junspa
dc.creatorMayes, Maureen D.spa
dc.creatorGorlova, Olga Y.spa
dc.creatorWakeland, Wardspa
dc.creatorRadstake, Timothyspa
dc.creatorMartin, Ezequielspa
dc.creatorMartin, Javierspa
dc.creatorSiminovitch, Katherinespa
dc.creatorSivils, Kathy L. Moserspa
dc.creatorGaffney, Patrick M.spa
dc.creatorLangefeld, Carl D.spa
dc.creatorHarley, John B.spa
dc.creatorKaufman, Kenneth M.spa
dc.date.accessioned2020-05-26T00:10:20Z
dc.date.available2020-05-26T00:10:20Z
dc.date.created2015spa
dc.description.abstractExploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10-49; OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3(P-valuesEU = 10-27-10-32, OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credibleset of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3. © The Author 2014.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/hmg/ddu455
dc.identifier.issn14602083
dc.identifier.issn09646906
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24223
dc.language.isoengspa
dc.publisherOxford University Pressspa
dc.relation.citationEndPage596
dc.relation.citationIssueNo. 2
dc.relation.citationStartPage582
dc.relation.citationTitleHuman Molecular Genetics
dc.relation.citationVolumeVol. 24
dc.relation.ispartofHuman Molecular Genetics, ISSN:14602083, 09646906, Vol.24, No.2 (2015); pp. 582-596spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84922444783&doi=10.1093%2fhmg%2fddu455&partnerID=40&md5=aebfde457becb0e467f237be31d23679spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordTranscription factorspa
dc.subject.keywordTranscription factor zbtb3spa
dc.subject.keywordsystemiceng
dc.subject.keywordsingle nucleotideeng
dc.subject.keywordhumaneng
dc.subject.keywordhumaneng
dc.subject.keywordhumaneng
dc.subject.keywordgeneticeng
dc.subject.keywordUnclassified drugspa
dc.subject.keywordDna binding proteinspa
dc.subject.keywordInterferon regulatory factorspa
dc.subject.keywordIrf5 proteineng
dc.subject.keywordKaryopherin betaspa
dc.subject.keywordTnpo3 proteineng
dc.subject.keywordZbtb3 proteineng
dc.subject.keywordAllelespa
dc.subject.keywordAncestry groupspa
dc.subject.keywordArticlespa
dc.subject.keywordAutoimmune diseasespa
dc.subject.keywordBayes theoremspa
dc.subject.keywordControlled studyspa
dc.subject.keywordDisease assessmentspa
dc.subject.keywordDna sequencespa
dc.subject.keywordEuropeanspa
dc.subject.keywordGenespa
dc.subject.keywordGene expressionspa
dc.subject.keywordGene locusspa
dc.subject.keywordGene mappingspa
dc.subject.keywordGenetic associationspa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordGenotypespa
dc.subject.keywordHaplotypespa
dc.subject.keywordHumanspa
dc.subject.keywordIrf5 genespa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordPrimary biliary cirrhosisspa
dc.subject.keywordPriority journalspa
dc.subject.keywordPromoter regionspa
dc.subject.keywordSjoegren syndromespa
dc.subject.keywordSystemic lupus erythematosusspa
dc.subject.keywordSystemic sclerosisspa
dc.subject.keywordTnpo3 genespa
dc.subject.keywordAutoimmune diseasespa
dc.subject.keywordCase control studyspa
dc.subject.keywordCohort analysisspa
dc.subject.keywordGeneticsspa
dc.subject.keywordMalespa
dc.subject.keywordSingle nucleotide polymorphismspa
dc.subject.keywordSystemic lupus erythematosusspa
dc.subject.keywordAutoimmune diseasesspa
dc.subject.keywordBayes theoremspa
dc.subject.keywordBeta karyopherinsspa
dc.subject.keywordCase-control studiesspa
dc.subject.keywordCohort studiesspa
dc.subject.keywordDna-binding proteinsspa
dc.subject.keywordHaplotypesspa
dc.subject.keywordHumansspa
dc.subject.keywordInterferon regulatory factorsspa
dc.subject.keywordLupus erythematosuseng
dc.subject.keywordMalespa
dc.subject.keywordPolymorphismeng
dc.subject.keywordPromoter regionseng
dc.titleThe IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably sharespa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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