Institute of Liver Studies, Liver Immunopathology, King's College London School of Medicine at King's College Hospital, London, UK.
J Autoimmun. 2012 May;38(2-3):J156-69. doi: 10.1016/j.jaut.2011.11.003. Epub 2011 Dec 15.
Twin studies are powerful tools to discriminate whether a complex disease is due to genetic or environmental factors. High concordance rates among monozygotic (MZ) twins support genetic factors being predominantly involved, whilst low rates are suggestive of environmental factors. Twin studies have often been utilised in the study of systemic and organ specific autoimmune diseases. As an example, type I diabetes mellitus has been investigated to establish that that disease is largely affected by genetic factors, compared to rheumatoid arthritis or scleroderma, which have a weaker genetic association. However, large twin studies are scarce or virtually non-existent in other autoimmune diseases which have been limited to few sets of twins and individual case reports. In addition to the study of the genetic and environmental contributions to disease, it is likely that twin studies will also provide data in regards to the clinical course of disease, as well as risk for development in related individuals. More importantly, genome-wide association studies have thus far reported genomic variants that only account for a minority of autoimmunity cases, and cannot explain disease discordance in MZ twins. Future research is therefore encouraged not only in the analysis of twins with autoimmune disease, but also in regards to epigenetic factors or rare variants that may be discovered with next-generation sequencing. This review will examine the literature surrounding twin studies in autoimmune disease including discussions of genetics and gender.
双胞胎研究是区分复杂疾病是由遗传因素还是环境因素引起的有力工具。同卵 (MZ) 双胞胎之间的高一致性率支持遗传因素起主要作用，而低一致性率则提示环境因素的作用。双胞胎研究常用于研究系统性和器官特异性自身免疫性疾病。例如，已经研究了 1 型糖尿病，以确定该疾病主要受遗传因素影响，而类风湿关节炎或硬皮病的遗传相关性较弱。然而，在其他自身免疫性疾病中，大型双胞胎研究很少或几乎不存在，这些疾病仅限于少数几对双胞胎和个别病例报告。除了研究遗传和环境因素对疾病的贡献外，双胞胎研究还可能提供有关疾病临床过程以及相关个体发病风险的信息。更重要的是，全基因组关联研究迄今为止报告的基因组变异仅占自身免疫病例的少数，并且不能解释 MZ 双胞胎之间的疾病不一致性。因此，鼓励未来不仅对自身免疫性疾病的双胞胎进行分析，还对表观遗传因素或可能通过下一代测序发现的罕见变异进行研究。这篇综述将检查自身免疫性疾病中双胞胎研究的文献，包括对遗传学和性别问题的讨论。
