Although small numbers of immune-mediated diseases are inherited due to rare genetic mutations, most are multifactorial diseases caused by multiple elements including genetic and environmental factors. In the case of autoimmune diseases, many disease-susceptibility genes, including several in the major histocompatibility gene complex, have been reported, and over the past 10 years, genome-wide association studies (GWAS) have been used to analyze disease-susceptibility loci in representative diseases. Furthermore, many disease susceptibility variants have been found to be related to gene expression levels. The expression of genes involved in disease pathogenesis is often cell type-specific, and this is closely related to epigenome alterations. Genomic information is present even before the onset of a disease and has a clear causal relationship to the disease (i.e., the outcome). Therefore, it is important to establish functional genetics in human immunology to understand the pathogenesis of diseases using these pieces of information. We can then apply these results to drug discovery. Here, we will review these issues, especially focusing on autoimmune diseases, and discuss current and future directions of human immune system research.

中文翻译：

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用于研究人类免疫系统的功能遗传学

虽然少数免疫介导的疾病是由于罕见的基因突变而遗传的，但大多数是由遗传和环境因素等多种因素引起的多因素疾病。就自身免疫性疾病而言，已报道了许多疾病易感基因，包括主要组织相容性基因复合物中的几个基因，并且在过去 10 年中，已使用全基因组关联研究 (GWAS) 来分析疾病易感性位点在代表性疾病中。此外，已发现许多疾病易感性变异与基因表达水平有关。参与疾病发病机制的基因表达通常是细胞类型特异性的，这与表观基因组的改变密切相关。基因组信息甚至在疾病发作之前就已经存在，并且与疾病（即结果）具有明确的因果关系。因此，重要的是在人类免疫学中建立功能遗传学，以利用这些信息了解疾病的发病机制。然后，我们可以将这些结果应用于药物发现。在这里，我们将回顾这些问题，特别是关注自身免疫性疾病，并讨论人类免疫系统研究的当前和未来方向。