Redefining the IBDs using genome-scale molecular phenotyping.
Redefining the IBDs using genome-scale molecular phenotyping.
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DOI：
10.1038/s41575-019-0118-x
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发表时间：
2019-05
期刊：
影响因子：
--
通讯作者：
Sheikh SZ
中科院分区：
文献类型：
--
作者：
Furey TS;Sethupathy P;Sheikh SZ
炎症性肠病（IBD）、克罗恩病和溃疡性结肠炎是由遗传易感个体对肠道微生物群的异常免疫应答引起的胃肠道慢性炎症性病症。IBD内和IBD间的疾病表现和进展，尤其是克罗恩病，在位置、炎症严重程度和其他表型方面高度异质。目前的临床分类无法准确预测疾病的病程和对治疗的反应。全基因组关联研究已经确定了超过240个赋予IBD风险的基因座，但这些发现的临床效用仍然不清楚，遗传变异导致疾病的机制在很大程度上是未知的。在过去的五年中，对肠道组织和粪便样本中全基因组基因表达、表观基因组特征和肠道微生物群组成的分析揭示了定义IBD亚型的不同分子特征，包括克罗恩病和溃疡性结肠炎。在这篇综述中，我们总结了在成人和儿童患者中发现不同IBD亚型的研究，这些亚型在某些情况下与不同的临床表型相关。我们认为，在大型队列中进行基因组规模的分子表型分析，不仅有助于进一步了解IBD的不同分子病因，而且有助于改善临床试验设计，以开发更个性化的疾病管理和治疗。
The inflammatory bowel diseases (IBDs), Crohn’s disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract resulting from an aberrant immune response to enteric microbiota in genetically susceptible individuals. Disease presentation and progression within and across IBDs, especially Crohn’s disease, is highly heterogeneous in location, severity of inflammation and other phenotypes. Current clinical classifications fail to accurately predict disease course and response to therapies. Genome-wide association studies have identified over 240 loci that confer risk of IBD, but the clinical utility of these findings remain unclear, and mechanisms by which the genetic variants contribute to disease are largely unknown. In the past five years, the profiling of genome-wide gene expression, epigenomic features and gut microbiota composition in intestinal tissue and faecal samples has uncovered distinct molecular signatures that define IBD subtypes, including within Crohn’s disease and ulcerative colitis. In this Review, we summarize studies in both adult and paediatric patients that have identified different IBD subtypes, which in some cases have been associated with distinct clinical phenotypes. We posit that genome-scale molecular phenotyping in large cohorts holds great promise not only to further our understanding of the diverse molecular causes of IBD but also for improving clinical trial designs to develop more personalized disease management and treatment.
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克罗恩病和溃疡性结肠炎表型的遗传决定因素：遗传关联研究。
DOI：
10.1016/s0140-6736(15)00465-1
发表时间：
2016-01-09
期刊：
Lancet (London, England)
影响因子：
--
作者：
Cleynen I;Boucher G;Jostins L;Schumm LP;Zeissig S;Ahmad T;Andersen V;Andrews JM;Annese V;Brand S;Brant SR;Cho JH;Daly MJ;Dubinsky M;Duerr RH;Ferguson LR;Franke A;Gearry RB;Goyette P;Hakonarson H;Halfvarson J;Hov JR;Huang H;Kennedy NA;Kupcinskas L;Lawrance IC;Lee JC;Satsangi J;Schreiber S;Théâtre E;van der Meulen-de Jong AE;Weersma RK;Wilson DC;International Inflammatory Bowel Disease Genetics Consortium;Parkes M;Vermeire S;Rioux JD;Mansfield J;Silverberg MS;Radford-Smith G;McGovern DP;Barrett JC;Lees CW
通讯作者：
Lees CW
影响因子：
29.4
作者：
Abraham C;Dulai PS;Vermeire S;Sandborn WJ
通讯作者：
Sandborn WJ
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Beres, Nra Judit;Kiss, Zoltan;Veres, Gabor
通讯作者：
Veres, Gabor
影响因子：
65.1
作者：
de Souza, Heitor S. P.;Fiocchi, Claudio;Iliopoulos, Dimitrios
通讯作者：
Iliopoulos, Dimitrios