dc.contributor.author | Mc Manus, Ross | en |
dc.date.accessioned | 2011-03-16T11:57:35Z | |
dc.date.available | 2011-03-16T11:57:35Z | |
dc.date.issued | 2011 | en |
dc.date.submitted | 2011 | en |
dc.identifier.citation | Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L, Westra HJ, Fehrmann RS, Kurreeman FA, Thomson B, Gupta N, Romanos J, McManus R, Ryan AW, Turner G, Brouwer E, Posthumus MD, Remmers EF, Tucci F, Toes R, Grandone E, Mazzilli MC, Rybak A, Cukrowska B, Coenen MJ, Radstake TR, van Riel PL, Li Y, de Bakker PI, Gregersen PK, Worthington J, Siminovitch KA, Klareskog L, Huizinga TW, Wijmenga C, Plenge RM, Meta-Analysis of Genome-Wide Association Studies in Celiac Disease and Rheumatoid Arthritis Identifies Fourteen Non-HLA Shared Loci., PLoS genetics, 7, 2, 2011, e1002004 | en |
dc.identifier.issn | 1553-7390 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/53321 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Epidemiology 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 |
dc.description.sponsorship | RMP was supported by grants from the NIH (R01-AR057108, R01-AR056768, U01-GM092691) and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. SR is supported by an NIH Career Development Award (1K08AR055688-01A1). FK is supported by a Marie Curie International Outgoing Fellowship for Career Development from the European Community's FP7 (Grant Agreement number PIOF-GA-2009-237280). The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources. The work presented is made possible by grants from the Coeliac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative, and partially funded by the Dutch Government (BSIK03009 to CW) and by the Netherlands Organisation for Scientific Research (NWO, VICI grant 918.66.620 to CW). LF received a Horizon Breakthrough grant from the Netherlands Genomics Initiative (93519031) and a VENI grant from NWO (ZonMW grant 916.10.135). AZ received a Rubicon grant from NWO (825.10.002). GT received a Ter Meulen Fund grant from the Royal Netherlands Academy of Arts and Sciences (KNAW). RMcM is supported by a Science Foundation Ireland Grant 09/IN.1/B2640. KAS is supported by a Canada Research Chair, Sherman Family Chair in Genomic Medicine, CIHR grants MOP79321 and IIN84042, and ORF grant RE01061. This work is partly supported by Coordination Theme 1 (Health) of the European Community's FP7, Grant Agreement number HEALTH-F2-2008-223404 (MASTERSWITCH project); by the EU FP6 supported AutoCure; and by the intramural program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. | en |
dc.format.extent | e1002004 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | PLoS genetics | en |
dc.relation.ispartofseries | 7 | en |
dc.relation.ispartofseries | 2 | en |
dc.rights | Y | en |
dc.subject | Genetics | en |
dc.subject | celiac disease (CD) | en |
dc.subject | rheumatoid arthritis (RA) | en |
dc.title | Meta-Analysis of Genome-Wide Association Studies in Celiac Disease and Rheumatoid Arthritis Identifies Fourteen Non-HLA Shared Loci. | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | National Institutes of Health (NIH) | en |
dc.contributor.sponsor | National Institutes of Health (NIH) | en |
dc.contributor.sponsor | National Institutes of Health (NIH) | en |
dc.contributor.sponsor | European Commission | en |
dc.contributor.sponsor | European Commission | en |
dc.contributor.sponsor | National Institutes of Health (NIH) | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/rmcmanus | en |
dc.identifier.rssinternalid | 71780 | en |
dc.identifier.doi | http://dx.doi.org/10.1371/journal.pgen.1002004 | en |
dc.relation.ecprojectid | info:eu-repo/grantAgreement/EC/FP7/HEALTH-F2-2008-223404 | |
dc.relation.ecprojectid | info:eu-repo/grantAgreement/EC/FP7/PIOF-GA-2009-237280 | |
dc.contributor.sponsorGrantNumber | U01-GM092691 | en |
dc.contributor.sponsorGrantNumber | R01-AR057108 | en |
dc.contributor.sponsorGrantNumber | R01-AR056768 | en |
dc.contributor.sponsorGrantNumber | PIOF-GA-2009-237280 | en |
dc.contributor.sponsorGrantNumber | HEALTH-F2-2008-223404 | en |
dc.contributor.sponsorGrantNumber | 1K08AR055688-01A1 | en |
dc.contributor.sponsorGrantNumber | 09/IN.1/B2640 | en |
dc.subject.TCDTheme | Genes & Society | en |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.subject.TCDTheme | International Development | en |
dc.identifier.rssuri | http://dx.doi.org/10.1371/journal.pgen.1002004 | en |