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.