The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Best Pract Res Clin Gastroenterol. 2014 Jun;28(3):373-86. doi: 10.1016/j.bpg.2014.04.009. Epub 2014 May 6.
The exact aetiology of Crohn's disease is unknown, though it is clear from early epidemiological studies that a combination of genetic and environmental risk factors contributes to an individual's disease susceptibility. Here, we review the history of gene-mapping studies of Crohn's disease, from the linkage-based studies that first implicated the NOD2 locus, through to modern-day genome-wide association studies that have discovered over 140 loci associated with Crohn's disease and yielded novel insights into the biological pathways underlying pathogenesis. We describe on-going and future gene-mapping studies that utilise next generation sequencing technology to pinpoint causal variants and identify rare genetic variation underlying Crohn's disease risk. We comment on the utility of genetic markers for predicting an individual's disease risk and discuss their potential for identifying novel drug targets and influencing disease management. Finally, we describe how these studies have shaped and continue to shape our understanding of the genetic architecture of Crohn's disease.
确切的病因尚未可知，尽管早期的流行病学研究清楚表明，遗传和环境风险因素的组合导致个体易患疾病。在这里，我们回顾了对克罗恩病的基因图谱研究的历史，从最初表明 NOD2 基因座的连锁研究，到现代全基因组关联研究，发现了 140 多个与克罗恩病相关的位点，并深入了解了发病机制的生物学途径。我们描述了正在进行和未来的基因图谱研究，这些研究利用下一代测序技术来确定致病变异，并确定克罗恩病风险背后的罕见遗传变异。我们还讨论了遗传标记用于预测个体疾病风险的实用性，并讨论了它们在识别新的药物靶点和影响疾病管理方面的潜力。最后，我们描述了这些研究如何塑造和继续塑造我们对克罗恩病遗传结构的理解。
