Genetic studies, including genome-wide association studies, have identified many common variants that are associated with autoimmune diseases. Strikingly, in addition to being frequently observed in healthy individuals, a number of these variants are shared across diseases with diverse clinical presentations. This highlights the potential for improved autoimmune disease understanding which could be achieved by characterising the mechanism by which variants lead to increased risk of disease. Of particular interest is the potential for identifying novel drug targets or of repositioning drugs currently used in other diseases. The majority of autoimmune disease variants do not alter coding regions and it is often difficult to generate a plausible hypothetical mechanism by which variants affect disease-relevant genes and pathways. Given the interest in this area, considerable effort has been invested in developing and applying appropriate methodologies. Two of the most important technologies in this space include both low- and high-throughput genomic perturbation using the CRISPR/Cas9 system and massively parallel reporter assays. In this review, we introduce the field of autoimmune disease functional genomics and use numerous examples to demonstrate the recent and potential future impact of these technologies.

遗传学研究，包括全基因组关联研究，已经确定了许多与自身免疫性疾病相关的常见变异。引人注目的是，除了在健康个体中经常观察到之外，其中许多变异在具有不同临床表现的疾病中也存在。这凸显了改善自身免疫性疾病理解的潜力，这可以通过表征变异导致疾病风险增加的机制来实现。特别令人感兴趣的是识别新药物靶点或重新定位目前用于其他疾病的药物的潜力。大多数自身免疫性疾病变异不会改变编码区，并且通常很难生成变异影响疾病相关基因和途径的合理的假设机制。鉴于人们对该领域的兴趣，在开发和应用适当的方法方面投入了大量的精力。该领域最重要的两项技术包括使用 CRISPR/Cas9 系统进行低通量和高通量基因组扰动以及大规模并行报告分析。在这篇综述中，我们介绍了自身免疫性疾病功能基因组学领域，并使用大量例子来证明这些技术的近期和未来潜在的影响。