Autoimmune diseases: insights from genome-wide association studies
Autoimmune diseases: insights from genome-wide association studies
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DOI：
10.1093/hmg/ddn246
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发表时间：
2008-10-15
影响因子：
3.5
通讯作者：
Rioux, John D.
中科院分区：
文献类型：
--
作者：
Lettre, Guillaume;Rioux, John D.
当个体自身的免疫系统攻击并破坏其健康细胞和组织时，就会发生自身免疫性疾病。尽管环境刺激显然会使人患上自身免疫性疾病，但基于双胞胎和家庭的研究表明，遗传因素在改变疾病风险方面也发挥着重要作用。由于其中许多疾病相对常见（欧洲人群中的患病率：0.01-11%）并且表现出复杂的遗传模式，因此许多对疾病风险影响不大的 DNA 序列变异会增加遗传负担。最近，HapMap项目的完成，加上新基因分型技术的发展，为人类遗传学家提供了必要的工具，以全面、公正的方式，在我们的基因组中寻找与许多自身免疫性疾病相关的DNA多态性。在此，我们回顾了利用全基因组关联研究 (GWAS) 识别乳糜泻、克罗恩病、多发性硬化症、类风湿性关节炎、系统性红斑狼疮和 1 型糖尿病遗传危险因素方面的最新进展。引人注目的是，GWAS 将与这些自身免疫性疾病相关的遗传风险变异的数量从 2006 年之前的 15 种增加到现在的 68 种。我们总结了这种新的遗传景观在这些疾病的发病机制方面给我们带来的启示，并强调了未来的一些突出挑战。最后，我们就如何最大程度地发挥这些基因发现对最重要的影响（即对于自身免疫性疾病患者）的影响进行了讨论。
Autoimmune diseases occur when an individual's own immune system attacks and destroys his or her healthy cells and tissues. Although it is clear that environmental stimuli can predispose someone to develop autoimmune diseases, twin- and family-based studies have shown that genetic factors also play an important role in modifying disease risk. Because many of these diseases are relatively common (prevalence in European-derived populations: 0.01-11%) and exhibit a complex mode of inheritance, many DNA sequence variants with modest effect on disease risk contribute to the genetic burden. Recently, the completion of the HapMap project, together with the development of new genotyping technologies, has given human geneticists the tools necessary to comprehensively, and in an unbiased manner, search our genome for DNA polymorphisms associated with many autoimmune diseases. Here we review recent progress made in the identification of genetic risk factors for celiac disease, Crohn's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and type-1 diabetes using genome-wide association studies (GWAS). Strikingly, GWAS have increased the number of genetic risk variants associated with these autoimmune diseases from 15 before 2006 to 68 now. We summarize what this new genetic landscape teaches us in terms of the pathogenesis of these diseases, and highlight some of the outstanding challenges ahead. Finally, we open a discussion on ways to best maximize the impact of these genetic discoveries where it matters the most, that is for autoimmune disease patients.