دورية أكاديمية
Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study
| العنوان: | Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study |
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| المؤلفون: | Cleynen, I., Boucher, G., Jostins, L., Schumm, L., Zeissig, S., Ahmad, T., Andersen, V., Andrews, J., Annese, V., Brand, S., Brant, S., Cho, J., Daly, M., Dubinsky, M., Duerr, R., Ferguson, L., Franke, A., Gearry, R., Goyette, P., Hakonarson, H. |
| المصدر: | http://dx.doi.org/10.1016/s0140-6736Test(15)00465-1. |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2016 |
| المجموعة: | The University of Adelaide: Digital Library |
| مصطلحات موضوعية: | Humans |
| الوصف: | Published Online October 19, 2015 ; Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0140-6736 1474-547X |
| العلاقة: | DK062431; DK062422; DK062429; DK062420; DK062432; DK062423; DK076984; DK084554; DK062429-S1; CA141743; PO1DK046763; U01 DK062418; The Lancet, 2016; 387(10014):156-167; http://hdl.handle.net/2440/98900Test; Andrews, J. [0000-0001-7960-2650] |
| DOI: | 10.1016/S0140-6736(15)00465-1 |
| الإتاحة: | https://doi.org/10.1016/S0140-6736Test(15)00465-1 https://doi.org/10.1016/s0140-6736Test(15)00465-1 http://hdl.handle.net/2440/98900Test |
| حقوق: | © Cleynen et al. Open Access article distributed under the terms of CC BY. |
| رقم الانضمام: | edsbas.618DA3A2 |
| قاعدة البيانات: | BASE |
| تدمد: | 01406736 1474547X |
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| DOI: | 10.1016/S0140-6736(15)00465-1 |