Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

被引:104
作者
Gutierrez-Achury, Javier [1 ]
Zhernakova, Alexandra [1 ]
Pulit, Sara L. [2 ]
Trynka, Gosia [3 ]
Hunt, Karen A. [4 ]
Romanos, Jihane [1 ]
Raychaudhuri, Soumya [5 ,6 ,7 ,8 ,9 ]
van Heel, David A. [4 ]
Wijmenga, Cisca [1 ]
de Balcker, Paul I. W. [2 ,10 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands
[2] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands
[3] Wellcome Trust Sanger Inst, Cambridge, England
[4] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England
[5] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Boston, MA USA
[7] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA
[8] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA
[9] Univ Manchester, Inst Inflammat & Repair, Ctr Musculoskeletal Res, Arthritis Res UK Epidemiol Unit, Manchester, Lancs, England
[10] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands
基金
美国国家卫生研究院; 欧洲研究理事会;
关键词
HERITABILITY; HLA; ASSOCIATION; HAPLOTYPE; VARIANTS;
D O I
10.1038/ng.3268
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and observed five new associations that account for 18% of the genetic risk. Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.
引用
收藏
页码:577 / 578
页数:2
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