Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Figure 1: Analysis of chromosome 4q27 region around rs13119723.


  1. Nistico, L. et al. Gut 55, 803–808 (2006).

    Article  CAS  Google Scholar 

  2. Karell, K. et al. Hum. Immunol. 64, 469–477 (2003).

    Article  CAS  Google Scholar 

  3. van Heel, D.A. & West, J. Gut 55, 1037–1046 (2006).

    Article  CAS  Google Scholar 

  4. Hunt, K.A. et al. Eur. J. Hum. Genet. 13, 440–444 (2005).

    Article  CAS  Google Scholar 

  5. Monsuur, A.J. et al. Nat. Genet. 37, 1341–1344 (2005).

    Article  CAS  Google Scholar 

  6. International HapMap Consortium. Nature 437, 1299–1320 (2005).

  7. Gabriel, S.B. et al. Science 296, 2225–2229 (2002).

    Article  CAS  Google Scholar 

  8. Sadlack, B. et al. Cell 75, 253–261 (1993).

    Article  CAS  Google Scholar 

  9. Monteleone, G. et al. Gastroenterology 128, 687–694 (2005).

    Article  CAS  Google Scholar 

  10. He, Q.Y. et al. Bioinformatics 22, 2189–2191 (2006).

    Article  CAS  Google Scholar 

  11. Yamanouchi, J. et al. Nat. Genet. 39, 329–337 (2007).

    Article  CAS  Google Scholar 

  12. Redon, R. et al. Nature 444, 444–454 (2006).

    Article  CAS  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to David A van Heel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

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)

Supplementary Methods (PDF 105 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing