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Newly identified genetic risk variants for celiac disease related to the immune response.

Karen A Hunt, Alexandra Zhernakova, Graham Turner, Graham A R Heap, Lude Franke, Marcel Bruinenberg, Jihane Romanos, Lotte C Dinesen, Anthony W Ryan, Davinder Panesar, Rhian Gwilliam, Fumihiko Takeuchi, William M McLaren, Geoffrey K T Holmes, Peter D Howdle, Julian R F Walters, David S Sanders, Raymond J Playford, Gosia Trynka, Chris J J Mulder, M Luisa Mearin, Wieke H M Verbeek, Valerie Trimble, Fiona M Stevens, Colm O'Morain, Nicholas P Kennedy, Dermot Kelleher, Daniel J Pennington, David P Strachan, Wendy L McArdle, Charles A Mein, Martin C Wapenaar, Panos Deloukas, Ralph McGinnis, Ross McManus, Cisca Wijmenga, David A van Heel
Nature Genetics 2008 April
Our 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 x 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.

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