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Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)

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dc.creatorHan, Shizhongspa
dc.creatorKim-Howard, Xanaspa
dc.creatorDeshmukh, Harshalspa
dc.creatorKamatani, Yoichirospa
dc.creatorViswanathan, Parvathispa
dc.creatorGuthridge, Joel M.spa
dc.creatorThomas, Kenazspa
dc.creatorKaufman, Kenneth M.spa
dc.creatorOjwang, Joshuaspa
dc.creatorRojas-Villarraga, Adrianaspa
dc.creatorBaca, Vicentespa
dc.creatorOrozco, Lorenaspa
dc.creatorRhodes, Benjaminspa
dc.creatorChoi, Chan-Bumspa
dc.creatorGregersen, Peter K.spa
dc.creatorMerrill, Joan T.spa
dc.creatorJames, Judith A.spa
dc.creatorGaffney, Patrick M.spa
dc.creatorMoser, Kathy L.spa
dc.creatorJacob, Chaim O.spa
dc.creatorKimberly, Robert P.spa
dc.creatorHarley, John B.spa
dc.creatorBae, Sang-Choelspa
dc.creatorAnaya, Juan-Manuelspa
dc.creatorAlarcón-Riquelme, Marta E.spa
dc.creatorMatsuda, Koichispa
dc.creatorVyse, Timothy J.spa
dc.creatorNath, Swapan K.spa
dc.date.accessioned2020-05-26T00:10:16Z
dc.date.available2020-05-26T00:10:16Z
dc.date.created2009spa
dc.description.abstractWe recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 × 10-8) and Hispanic-Americans (P = 2.9 × 10-5). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log10Bayes factor=20, P = 6.17 × 10-24). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 × 10-8), Colombian (P = 3.6 × 10-7), Mexican (P = 0.002), as well as two independent sets of trios from UK (P TDT = 1.4 × 10-5) and Mexico (P TDT = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P meta = 7.1 × 10-50, odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM- SLE association, especially in European- and African-derived populations, but not in Asian populations. © The Author 2009. Published by Oxford University Press. All rights reserved.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/hmg/ddp007
dc.identifier.issn14602083
dc.identifier.issn09646906
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/24221
dc.language.isoengspa
dc.relation.citationEndPage1180
dc.relation.citationIssueNo. 6
dc.relation.citationStartPage1171
dc.relation.citationTitleHuman Molecular Genetics
dc.relation.citationVolumeVol. 18
dc.relation.ispartofHuman Molecular Genetics, ISSN:14602083, 09646906, Vol.18, No.6 (2009); pp. 1171-1180spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-61849093275&doi=10.1093%2fhmg%2fddp007&partnerID=40&md5=4455104b301546fe8dfcaa6e5b03c9b3spa
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.keywordAlpha integrinspa
dc.subject.keywordsystemiceng
dc.subject.keywordAlpha m integrinspa
dc.subject.keywordsingle nucleotideeng
dc.subject.keywordAlpha x integrinspa
dc.subject.keywordGene productspa
dc.subject.keywordIntegrinspa
dc.subject.keywordProtein trim2spa
dc.subject.keywordUnclassified drugspa
dc.subject.keywordAfrican americanspa
dc.subject.keywordArticlespa
dc.subject.keywordControlled studyspa
dc.subject.keywordEuropean americanspa
dc.subject.keywordExonspa
dc.subject.keywordFemalespa
dc.subject.keywordGene frequencyspa
dc.subject.keywordGene replicationspa
dc.subject.keywordGene structurespa
dc.subject.keywordGenetic associationspa
dc.subject.keywordGenetic codespa
dc.subject.keywordGenetic susceptibilityspa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordGeographic distributionspa
dc.subject.keywordGeographic originspa
dc.subject.keywordHaplotypespa
dc.subject.keywordHumanspa
dc.subject.keywordJapanspa
dc.subject.keywordKoreaspa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordMalespa
dc.subject.keywordPriority journalspa
dc.subject.keywordRace differencespa
dc.subject.keywordSystemic lupus erythematosusspa
dc.subject.keywordAllelesspa
dc.subject.keywordAntigens, cd11bspa
dc.subject.keywordAsian continental ancestry groupspa
dc.subject.keywordBayes theoremspa
dc.subject.keywordCase-control studiesspa
dc.subject.keywordColombiaspa
dc.subject.keywordDemographyspa
dc.subject.keywordEuropean continental ancestry groupspa
dc.subject.keywordFemalespa
dc.subject.keywordGenetic predisposition to diseasespa
dc.subject.keywordGreat britainspa
dc.subject.keywordHaplotypesspa
dc.subject.keywordHispanic americansspa
dc.subject.keywordHumansspa
dc.subject.keywordJapanspa
dc.subject.keywordKoreaspa
dc.subject.keywordLinkage disequilibriumspa
dc.subject.keywordLupus erythematosuseng
dc.subject.keywordMalespa
dc.subject.keywordMeta-analysis as topicspa
dc.subject.keywordMexicospa
dc.subject.keywordPolymorphismeng
dc.subject.keywordReproducibility of resultsspa
dc.titleEvaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)spa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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