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Newly identified genetic risk variants for celiac disease related to the immune response
journal contribution
posted on 2023-05-17, 08:09 authored by Hunt, KA, Zhernakova, A, Turner, G, Heap, GAR, Franke, L, Bruinenberg, M, Romanos, J, Dinesen, LC, Ryan, A W, Panesar, D, Gwilliam, R, Takeuchi, F, McLaren, WM, Holmes, GKT, Howdle, PD, Walters, JRF, Sanders, DS, Playford, RJ, Trynka, G, Mulder, CJJ, Mearin, ML, Verbeek, WHM, Trimble, V, Stevens, FM, O'Morain, C, Kennedy, NP, Kelleher, D, Pennington, DJ, Strachan, DP, McArdle, WL, Mein, CA, Wapenaar, MC, Deloukas, P, McGinnis, R, McManus, R, Wijmenga, C, van Heel, DAOur genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 × 10 -7). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways. © 2008 Nature Publishing Group.
History
Publication title
Nature GeneticsVolume
40Issue
4Pagination
395-402ISSN
1061-4036Department/School
College Office - College of Health and MedicinePublisher
Nature Publishing GroupPlace of publication
345 Park Ave South, New York, USA, Ny, 10010-1707Repository Status
- Restricted
