A genome-wide association scan in individuals with Crohn's disease by the Wellcome Trust Case Control Consortium detected strong association at four novel loci. We tested 37 SNPs from these and other loci for association in an independent case-control sample. We obtained replication for the autophagy-inducing IRGM gene on chromosome 5q33.1 (replication P = 6.6 × 10−4, combined P = 2.1 × 10−10) and for nine other loci, including NKX2-3, PTPN2 and gene deserts on chromosomes 1q and 5p13.
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Hugot, J.P. et al. Nature 411, 599–603 (2001).
Ogura, Y. et al. Nature 411, 603–606 (2001).
Duerr, R.H. et al. Science 314, 1461–1463 (2006).
Hampe, J. et al. Nat. Genet. 39, 207–211 (2007).
Wellcome Trust Case Control Consortium. Nature 447, 661–678 (2007).
Bekpen, C. et al. Genome Biol. 6, R92.1–R92.18 (2005).
Singh, S.B. et al. Science 313, 1438–1441 (2006).
Collazo, C.M. et al. J. Exp. Med. 194, 181–187 (2001).
Libioulle, C. et al. PLoS Genet 3, e58 (2007).
Pabst, O. et al. EMBO J 19, 2015–2023 (2000).
Todd, J. et al. Nat. Genet. advance online publication 6 June 2007 (doi:10.1038/ng2068).
Rioux, J.D. et al. Nat. Genet. 39, 596–604 (2007).
Zwiers, A. et al. Genes Immun. 5, 675–677 (2004).
Cargill, M. et al. Am. J. Hum. Genet. 80, 273–290 (2007).
Rioux, J.D. et al. Nat. Genet. 29, 223–228 (2001).
We acknowledge use of DNA from the 1958 British Birth Cohort collection (R. Jones, S. Ring, W. McArdle and M. Pembrey), funded by the UK MRC (grant G0000934) and The Wellcome Trust (grant 068545/Z/02). We also acknowledge the National Association for Colitis and Crohn's disease and the Wellcome Trust for supporting the case DNA collections and UCB Pharma for supporting this study with an unrestricted educational grant. We thank D. Kelberman, all subjects who contributed samples and consultants and nursing staff across the UK who helped with recruitment of study subjects.
The authors declare no competing financial interests.
Details of Crohn's disease cases. (PDF 18 kb)
SNPs with converging allele frequencies. (PDF 35 kb)
SNP genotype call rates. (PDF 28 kb)
SNP genotype counts. (PDF 33 kb)
IRGM resequencing primers. (PDF 14 kb)
Association with Crohn's disease subphenotypes. (PDF 24 kb)
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