Published.
Article abstract
Nature Genetics
Published online: 2 March 2008 | doidoidoi:10.1038/ng.102
Newly identified genetic risk variants for celiac disease related to the immune response
Karen A Hunt1, Alexandra Zhernakova2, Graham Turner3, Graham A R Heap1, Lude Franke2, Marcel Bruinenberg4, Jihane Romanos4, Lotte C Dinesen5, Anthony W Ryan3, Davinder Panesar1, Rhian Gwilliam6, Fumihiko Takeuchi6, William M McLaren6, Geoffrey K T Holmes7, Peter D Howdle8, Julian R F Walters9, David S Sanders10, Raymond J Playford1, Gosia Trynka4, Chris J J Mulder11, M Luisa Mearin12,13, Wieke H M Verbeek11, Valerie Trimble3, Fiona M Stevens14, Colm O'Morain3, Nicholas P Kennedy3, Dermot Kelleher3, Daniel J Pennington1, David P Strachan15, Wendy L McArdle16, Charles A Mein17, Martin C Wapenaar4, Panos Deloukas6, Ralph McGinnis6, Ross McManus3,18, Cisca Wijmenga2,4,18 & David A van Heel1,18
Abstract
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
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.
Nature Genetics
Published online: 2 March 2008 | doidoidoi:10.1038/ng.102
Newly identified genetic risk variants for celiac disease related to the immune response
Karen A Hunt1, Alexandra Zhernakova2, Graham Turner3, Graham A R Heap1, Lude Franke2, Marcel Bruinenberg4, Jihane Romanos4, Lotte C Dinesen5, Anthony W Ryan3, Davinder Panesar1, Rhian Gwilliam6, Fumihiko Takeuchi6, William M McLaren6, Geoffrey K T Holmes7, Peter D Howdle8, Julian R F Walters9, David S Sanders10, Raymond J Playford1, Gosia Trynka4, Chris J J Mulder11, M Luisa Mearin12,13, Wieke H M Verbeek11, Valerie Trimble3, Fiona M Stevens14, Colm O'Morain3, Nicholas P Kennedy3, Dermot Kelleher3, Daniel J Pennington1, David P Strachan15, Wendy L McArdle16, Charles A Mein17, Martin C Wapenaar4, Panos Deloukas6, Ralph McGinnis6, Ross McManus3,18, Cisca Wijmenga2,4,18 & David A van Heel1,18
Abstract
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
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.