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

Hunt, Karen A
Zhernakova, Alexandra
Turner, Graham
Heap, Graham A R
Franke, Lude
Bruinenberg, Marcel
Romanos, Jihane
Dinesen, Lotte C
Ryan, Anthony W
Panesar, Davinder
... show 10 more
Hunt, Karen A; Zhernakova, Alexandra; Turner, Graham; Heap, Graham A R; Franke, Lude; Bruinenberg, Marcel; Romanos, Jihane; Dinesen, Lotte C; Ryan, Anthony W; Panesar, Davinder; Gwilliam, Rhian; Takeuchi, Fumihiko; McLaren, William M; Holmes, Geoffrey K T; Howdle, Peter D; Walters, Julian R F; Sanders, David S; Playford, Raymond J; Trynka, Gosia; Mulder, Chris J J; Mearin, M Luisa; Verbeek, Wieke H M; Trimble, Valerie; Stevens, Fiona M; O'Morain, Colm; Kennedy, Nicholas P; Kelleher, Dermot; Pennington, Daniel J; Strachan, David P; McArdle, Wendy L; Mein, Charles A; Wapenaar, Martin C; Deloukas, Panos; McGinnis, Ralph; McManus, Ross; Wijmenga, Cisca; van Heel, David A (2008). Newly identified genetic risk variants for celiac disease related to the immune response. Nature Genetics 40 (4), 395-402
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.
Springer Nature
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