Human Molecular Genetics Advance Access originally published online on July 31, 2009
Human Molecular Genetics 2009 18(21):4219-4225; doi:10.1093/hmg/ddp364
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Replication of celiac disease UK genome-wide association study results in a US population
1 Department of Epidemiology, University of California Irvine, Irvine, CA, USA 2 Department of Gastroenterology, The Mayo Clinic, Rochester, MN, USA 3 Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK
* To whom correspondence should be addressed at: University of California Irvine, 224 Irvine Hall, Irvine, CA 92697-7550, USA. Tel: +1 9498245769; Fax: +1 9498248482; Email: sneuhaus{at}uci.edu
Received April 17, 2009; Revised July 17, 2009; Accepted July 29, 2009
Celiac disease is a common disease with a prevalence of 
1%. A recent genome-wide association study (GWAS) and follow-up study identified eight loci significantly associated with celiac disease risk. We genotyped the top 1020 non-HLA single nucleotide polymorphisms (SNPs) from the GWAS study that were genotyped in the previous follow-up study. After quality control assessments, 975 SNPs were analyzed for association with 906 celiac disease cases and 3819 controls, using logistic regression. Additional genotype data were generated by imputation and analyzed across the regions showing the strongest statistical evidence for association. Twenty SNPs were associated with celiac disease with P < 0.01 in the current study as well as in the previous follow-up study, of which 16 had P < 0.001 and 11 had P < 1 x 10–11. Five of eight regions identified in the follow-up study were strongly associated with celiac disease, including regions on 1q31, 3q25, 3q28, 4q27 and 12q24. The strongest associations were at 4q27, the region most strongly associated in the GWAS and follow-up study and containing IL2 and IL21, and at 3q28 harboring LPP. In addition, we provide new evidence for an association, not previously reported, on 2q31 harboring a strong candidate gene, ITGA4. In conclusion, in this first follow-up study of celiac cases from the USA, we provide additional evidence that five of eight previously identified regions harbor risk alleles for celiac disease, and new evidence for an association on 2q31. The underlying functional mutations responsible for these replicated associations need to be identified.