Authors
Alexandra Zhernakova, Eli A Stahl, Gosia Trynka, Soumya Raychaudhuri, Eleanora A Festen, Lude Franke, Harm-Jan Westra, Rudolf SN Fehrmann, Fina AS Kurreeman, Brian Thomson, Namrata Gupta, Jihane Romanos, Ross McManus, Anthony W Ryan, Graham Turner, Elisabeth Brouwer, Marcel D Posthumus, Elaine F Remmers, Francesca Tucci, Rene Toes, Elvira Grandone, Maria Cristina Mazzilli, Anna Rybak, Bozena Cukrowska, Marieke JH Coenen, Timothy RDJ Radstake, Piet LCM van Riel, Yonghong Li, Paul IW De Bakker, Peter K Gregersen, Jane Worthington, Katherine A Siminovitch, Lars Klareskog, Tom WJ Huizinga, Cisca Wijmenga, Robert M Plenge
Publication date
2011/2/24
Journal
PLoS genetics
Volume
7
Issue
2
Pages
e1002004
Publisher
Public Library of Science
Description
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 (Pcombined = 1.2×10−12), rs864537 near CD247 (Pcombined = 2.2×10−11), rs2298428 near UBE2L3 (Pcombined = 2.5×10−10), and rs11203203 near UBASH3A (Pcombined = 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 …
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