Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
Department of Medicine and Cambridge Institute for Medical Research, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK; Translational Research in Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
Lancet Gastroenterol Hepatol. 2017 Mar;2(3):224-234. doi: 10.1016/S2468-1253(16)30111-X. Epub 2017 Feb 9.
The study of the genetic underpinnings of inflammatory bowel disease has made great progress since the identification of NOD2 as a major susceptibility gene. Novel genotyping and sequencing technologies have led to the discovery of 242 common susceptibility loci, 45 of which have been fine-mapped to statistically conclusive causal variants; 50 genes associated with very-early-onset inflammatory disease have been identified. The evolving genetic architecture of inflammatory bowel disease has deepened our understanding of its pathogenesis through identification of major disease associated pathways-knowledge that has the potential to indicate novel drug targets or markers for personalised medicine. However, many causal variants have yet to be identified, and a large proportion of missing heritability still needs to be accounted for. In addition, the medical and scientific communities are probably not yet fully harnessing the power of these genetic discoveries.
自从 NOD2 被确定为主要易感基因以来，炎症性肠病的遗传基础研究取得了很大进展。新型基因分型和测序技术已经发现了 242 个常见易感位点，其中 45 个已经被精细映射到具有统计学结论的因果变异；已经确定了 50 个与非常早发性炎症性疾病相关的基因。炎症性肠病不断发展的遗传结构通过鉴定主要疾病相关途径加深了我们对其发病机制的理解——这一知识有可能为新药靶点或个体化医学的标志物提供指示。然而，许多因果变异仍有待确定，大量的遗传缺失仍需要解释。此外，医疗和科学界可能尚未充分利用这些遗传发现的力量。
