Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease

被引：197

作者：

Lee, James C. ^{[1
]}

Biasci, Daniele ^{[1
]}

Roberts, Rebecca ^{[2
]}

Gearry, Richard B. ^{[2
]}

Mansfield, John C. ^{[3
]}

Ahmad, Tariq ^{[4
]}

Prescotts, Natalie J. ^{[5
]}

Satsangi, Jack ^{[6
]}

Wilson, David C. ^{[7
]}

Jostins, Luke ^{[8
]}

Anderson, Carl A. ^{[9
]}

Traherne, James A. ^{[10
]}

Lyons, Paul A. ^{[1
]}

Parkes, Miles ^{[1
]}

Smith, Kenneth G. C. ^{[1
]}

机构：

[1] Univ Cambridge, Sch Clin Med, Addenbrookes Hosp, Dept Med, Cambridge, England

[2] Univ Otago, Dept Med, Christchurch, New Zealand

[3] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England

[4] Univ Exeter, Sch Med, Exeter, Devon, England

[5] Kings Coll London, Fac Life Sci & Med, Dept Med & Mol Genet, London, England

[6] Univ Edinburgh, Western Gen Hosp, Sch Mol & Clin Med, Gastrointestinal Unit,Div Med Sci, Edinburgh, Midlothian, Scotland

[7] Univ Edinburgh, Royal Hosp Sick Children, Coll Med & Vet Med, Paediat Gastroenterol & Nutr Child Life & Hlth, Edinburgh, Midlothian, Scotland

[8] Univ Oxford, Wellcome Trust Ctr Human Genet, Headington, England

[9] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England

[10] Univ Cambridge, Dept Pathol, Cambridge, England

来源：

NATURE GENETICS | 2017年 / 49卷 / 02期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

INFLAMMATORY-BOWEL-DISEASE; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; ULCERATIVE-COLITIS; QUANTITATIVE TRAITS; RISK; VARIANTS; PREDICTION; PHENOTYPES; SEVERITY;

D O I：

10.1038/ng.3755

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

For most immune-mediated diseases, the main determinant of patient well-being is not the diagnosis itself but instead the course that the disease takes over time (prognosis)(1-3). Prognosis may vary substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis(4-6), but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants(7-13). To better characterize how genetic variation influences disease prognosis, we performed a within cases genome-wide association study in two cohorts of patients with Crohn's disease. We identified four genome-wide significant loci, none of which showed any association with disease susceptibility. Conversely, the aggregated effect of all 170 disease susceptibility loci was not associated with disease prognosis. Together, these data suggest that the genetic contribution to prognosis in Crohn's disease is largely independent of the contribution to disease susceptibility and point to a biology of prognosis that could provide new therapeutic opportunities.

引用

页码：262 / 268

页数：7

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