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dc.contributor.authorZhernakova, Alexandra
dc.contributor.authorStahl, Eli A.
dc.contributor.authorTrynka, Gosia
dc.contributor.authorFesten, Eleanora A.
dc.contributor.authorFranke, Lude
dc.contributor.authorWestra, Harm-Jan
dc.contributor.authorFehrmann, Rudolf S. N.
dc.contributor.authorKurreeman, Fina A. S.
dc.contributor.authorThomson, Brian
dc.contributor.authorGupta, Namrata
dc.contributor.authorRomanos, Jihane
dc.contributor.authorMcManus, Ross
dc.contributor.authorRyan, Anthony W.
dc.contributor.authorTurner, Graham
dc.contributor.authorBrouwer, Elisabeth
dc.contributor.authorPosthumus, Marcel D.
dc.contributor.authorRemmers, Elaine F.
dc.contributor.authorTucci, Francesca
dc.contributor.authorToes, Rene
dc.contributor.authorGrandone, Elvira
dc.contributor.authorMazzilli, Maria Cristina
dc.contributor.authorRybak, Anna
dc.contributor.authorCukrowska, Bozena
dc.contributor.authorCoenen, Marieke J. H.
dc.contributor.authorRadstake, Timothy R. D. J.
dc.contributor.authorvan Riel, Piet L. C. M.
dc.contributor.authorLi, Yonghong
dc.contributor.authorGregersen, Peter K.
dc.contributor.authorWorthington, Jane
dc.contributor.authorSiminovitch, Katherine A.
dc.contributor.authorKlareskog, Lars
dc.contributor.authorHuizinga, Tom W. J.
dc.contributor.authorWijmenga, Cisca
dc.contributor.authorRaychaudhuri, Soumya
dc.contributor.authorde Bakker, Paul I Wen
dc.contributor.authorPlenge, Robert M.
dc.date.accessioned2011-12-06T04:40:21Z
dc.date.issued2011
dc.identifier.citationZhernakova, Alexandra, Eli A. Stahl, Gosia Trynka, Soumya Raychaudhuri, Eleanora A. Festen, Lude Franke, Harm-Jan Westra, et al. 2011. Meta-Analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genetics 7(2): e1002004.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5360624
dc.description.abstractEpidemiology and candidate gene studies indicate a shared genetic basis for celiac disease (CD) and rheumatoid arthritis (RA), but the extent of this sharing has not been systematically explored. Previous studies demonstrate that 6 of the established non-HLA CD and RA risk loci (out of 26 loci for each disease) are shared between both diseases. We hypothesized that there are additional shared risk alleles and that combining genome-wide association study (GWAS) data from each disease would increase power to identify these shared risk alleles. We performed a meta-analysis of two published GWAS on CD (4,533 cases and 10,750 controls) and RA (5,539 cases and 17,231 controls). After genotyping the top associated SNPs in 2,169 CD cases and 2,255 controls, and 2,845 RA cases and 4,944 controls, 8 additional SNPs demonstrated P<5×10\(^{−8}\) in a combined analysis of all 50,266 samples, including four SNPs that have not been previously confirmed in either disease: rs10892279 near the DDX6 gene (P\(_{combined}\) = 1.2×10\(^{−12}\)), rs864537 near CD247 (P\(_{combined}\) = 2.2×10\(^{−11}\)), rs2298428 near UBE2L3 (P\(_{combined}\) = 2.5×10\(^{−10}\)), and rs11203203 near UBASH3A (P\(_{combined}\) = 1.1×10\(^{−8}\)). We also confirmed that 4 gene loci previously established in either CD or RA are associated with the other autoimmune disease at combined P<5×10\(^{−8}\) (SH2B3, 8q24, STAT4, and TRAF1-C5). From the 14 shared gene loci, 7 SNPs showed a genome-wide significant effect on expression of one or more transcripts in the linkage disequilibrium (LD) block around the SNP. These associations implicate antigen presentation and T-cell activation as a shared mechanism of disease pathogenesis and underscore the utility of cross-disease meta-analysis for identification of genetic risk factors with pleiotropic effects between two clinically distinct diseases.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1002004en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044685/pdf/en_US
dash.licenseLAA
dc.subjectcomputational biologyen_US
dc.subjectpopulation geneticsen_US
dc.subjectgenetics of diseaseen_US
dc.subjectgenetics of the immune systemen_US
dc.subjectclinical immunologyen_US
dc.subjectclinical geneticsen_US
dc.titleMeta-Analysis of Genome-Wide Association Studies in Celiac Disease and Rheumatoid Arthritis Identifies Fourteen Non-HLA Shared Locien_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorde Bakker, Paul I Wen
dc.date.available2011-12-06T04:40:21Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pgen.1002004*
dash.authorsorderedfalse
dash.contributor.affiliatedde Bakker, Paul
dash.contributor.affiliatedRaychaudhuri, Soumya
dash.contributor.affiliatedPlenge, Robert M.


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