Abstract
We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 × 10−7) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5′ of IL21; meta-analysis P = 1.3 × 10−14, odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.
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Acknowledgements
We thank C.A. Mein and the Barts and The London Genome Centre for advice and genotyping support; D. Simpkin, T. Dibling and C. Hand for genotyping (Sanger Institute); M.J. Caulfield for advice on study design; D.P. Kelsell for comments on the manuscript; D. Strachan and W.L. McArdle for 1958 Birth Cohort samples; A. Monsuur for patient recruitment; G. Meijer and J. Meijer for histology review; K. Duran for DNA extraction; H. van Someren for clinical database management (The Netherlands); A. Ryan, G. Turner, M. Abuzakouk, N. Kennedy, F. Stevens and C. O'Morain for patient and control recruitment and sample management (Ireland). We thank J. Loveland for EST annotation and checking. We thank the Wellcome Trust Centre for Human Genetics, University of Oxford, for computing facilities. We thank all affected individuals and controls for participating in this study. We acknowledge funding from Coeliac UK; the Coeliac Disease Consortium (an innovative cluster approved by The Netherlands Genomics Initiative and partly funded by the Dutch government (grant BSIK03009)); The Netherlands Genomics Initiative (grant 050-72-425); The Netherlands Organization for Scientific Research (grant 901-04-219); the Science Foundation Ireland and the Wellcome Trust (GR068094MA Clinician Scientist Fellowship to D.A.v.H.; New Blood Fellowship to R.M. and support for the work of R.McG. and P.D.). The authors acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02.
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Supplementary information
Supplementary Fig. 1
Summary of genome-wide association scan results. (PDF 1408 kb)
Supplementary Fig. 2
Linkage disequilibrium and haplotype analysis of the 4q27 region. (PDF 795 kb)
Supplementary Fig. 3
Quantitative RT-PCR analysis of expression of genes in the 4q27 region in duodenal tissue. (PDF 63 kb)
Supplementary Table 1
Characteristics of subjects. (PDF 16 kb)
Supplementary Table 2
Classical HLA type and rs2187668 genotype. (PDF 15 kb)
Supplementary Table 3
Genome-wide association and replication results. (PDF 82 kb)
Supplementary Table 4
4q27 SNPs and haplotypes in three collections. (PDF 142 kb)
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van Heel, D., Franke, L., Hunt, K. et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet 39, 827–829 (2007). https://doi.org/10.1038/ng2058
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DOI: https://doi.org/10.1038/ng2058
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