Rheumatoid arthritis (RA) is the most common inflammatory arthritis and exhibits genetic overlap with other autoimmune and inflammatory disorders. Although predominant associations with the HLA-DRB1 locus have been known for decades, recent data have revealed additional insight into the likely causative variants within HLA-DRB1 as well as within other HLA loci that contribute to disease risk. In addition, more than 100 common variants in non-HLA loci have been implicated in disease susceptibility. Genetic factors are involved not only in the development of RA, but also with various disease subphenotypes, including production and circulating levels of autoantibodies and joint destruction. The major current challenge is to integrate these new data into a precise understanding of disease pathogenesis, including the critical cell types and molecular networks involved as well as interactions with environmental factors. We predict that delineating the functional effects of genetic variants is likely to drive new diagnostic and therapeutic approaches to the disease.

中文翻译：

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定义类风湿关节炎遗传基础的最新进展。

类风湿关节炎（RA）是最常见的炎症性关节炎，与其他自身免疫性疾病和炎症性疾病表现出遗传重叠。尽管与HLA-DRB1基因座的主要联系已为人所知，但最近的数据揭示了对HLA-DRB1以及其他HLA基因座中可能引起疾病风险的可能致病变异的更多见解。另外，非HLA基因座中的100多个常见变体与疾病的易感性有关。遗传因素不仅与RA的发展有关，而且与多种疾病亚型有关，包括自身抗体的产生和循环水平以及关节破坏。当前的主要挑战是将这些新数据整合到对疾病发病机理的精确了解中，包括所涉及的关键细胞类型和分子网络以及与环境因素的相互作用。我们预测，描述遗传变异的功能作用可能会推动对该疾病的新诊断和治疗方法。