We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P-GWAS < 10(-4)... Show moreWe performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P-GWAS < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P-combined < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression. Show less
OBJECTIVES: /st> The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis (RA). Since genetic risk factors tend to overlap with several autoimmune... Show moreOBJECTIVES: /st> The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis (RA). Since genetic risk factors tend to overlap with several autoimmune diseases, a study was undertaken to investigate whether this region is associated with type 1 diabetes (TID), celiac disease (CD), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). METHODS: /st> The most consistently associated SNP, rs10818488, was genotyped in a total of 735 patients with T1D, 1049 with CD, 367 with SSc, 746 with SLE and 3494 ethnically- and geographically-matched healthy individuals. The replication sample set consisted of 99 patients with T1D, 272 with SLE and 482 healthy individuals from Crete. RESULTS: /st> A significant association was detected between the rs10818488 A allele and T1D (OR 1.14, p=0.027) and SLE (OR 1.16, p=0.016), which was replicated in 99 patients with T1D, 272 with SLE and 482 controls from Crete (OR 1.64, p=0.002; OR 1.43, p=0.002, respectively). Joint analysis of all patients with T1D (N=961) and all patients with SLE (N=1018) compared with 3976 healthy individuals yielded an allelic common OR of 1.19 (p=0.002) and 1.22 (p=2.6x10(-4)), respectively. However, combining our dataset with the T1D sample set from the WTCCC resulted in a non-significant association (OR 1.06, p=0.087). In contrast, previously unpublished results from the SLEGEN study showed a significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02x10(-6)) in a total of 1577 patients with SLE and 4215 healthy individuals. CONCLUSION: /st> A significant association was found for the TRAF1-C5 locus in SLE, implying that this region lies in a pathway relevant to multiple autoimmune diseases. Show less
Objectives The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis (RA). Since genetic risk factors tend to overlap with several autoimmune diseases, a... Show moreObjectives The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis (RA). Since genetic risk factors tend to overlap with several autoimmune diseases, a study was undertaken to investigate whether this region is associated with 1 diabetes (TID), celiac disease (CD), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Methods The most consistently associated SNP, rs10818488, was genotyped in a total of 735 patients with T1D, 1049 with CD, 367 with SSc, 746 with SLE and 3494 ethnically- and geographically-matched healthy individuals. The replication sample set consisted of 99 patients with T1D, 272 with SLE and 482 healthy individuals from Crete. Results A significant association was detected between the rs10818488 A allele and T1D (OR 1.14, p=0.027) and SLE (OR 1.16, p=0.016), which was replicated in 99 patients with T1D, 272 with SLE and 482 controls from Crete (OR 1.64, p=0.002; OR 1.43, p=0.002, respectively). Joint analysis of all patients with T1D (N=961) and all patients with SLE (N=1018) compared with 3976 healthy individuals yielded an allelic common OR of 1.19 (p=0.002) and 1.22 (p=2.6x10(-4)), respectively. However, combining our dataset with the T1D sample set from the WTCCC resulted in a nonsignificant association (OR 1.06, p=0.087). In contrast, previously unpublished results from the SLEGEN study showed a significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02x10(-6)) in a total of 1577 patients with SLE and 4215 healthy individuals. Conclusion A significant association was found for the TRAF1-C5 locus in SLE, implying that this region lies in a pathway relevant to multiple autoimmune diseases. Show less
