Department of Biology, Kyung Hee University, Seoul, Republic of Korea.
Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
Semin Immunopathol. 2022 Jan;44(1):29-46. doi: 10.1007/s00281-021-00900-w. Epub 2021 Nov 3.
Systemic lupus erythematosus (SLE) is a polygenic chronic autoimmune disease leading to multiple organ damage. A large heritability of up to 66% is estimated in SLE, with roughly 180 reported susceptibility loci that have been identified mostly by genome-wide association studies (GWASs) and account for approximately 30% of genetic heritability. A vast majority of risk variants reside in non-coding regions, which makes it quite challenging to interpret their functional implications in the SLE-affected immune system, suggesting the importance of understanding cell type-specific epigenetic regulation around SLE GWAS variants. The latest genetic studies have been highly fruitful as several dozens of SLE loci were newly discovered in the last few years and many loci have come to be understood in systemic approaches integrating GWAS signals with other biological resources. In this review, we summarize SLE-associated genetic variants in both the major histocompatibility complex (MHC) and non-MHC loci, examining polygenetic risk scores for SLE and their associations with clinical features. Finally, variant-driven pathogenetic functions underlying genetic associations are described, coupled with discussion about challenges and future directions in genetic studies on SLE.
系统性红斑狼疮（SLE）是一种多基因慢性自身免疫性疾病，可导致多器官损伤。SLE 的遗传率高达 66%，通过全基因组关联研究（GWAS）已确定了大约 180 个易感位点，这些易感位点约占遗传率的 30%。大多数风险变异位于非编码区域，这使得解释它们在受 SLE 影响的免疫系统中的功能意义具有很大的挑战性，这表明了解 SLE GWAS 变异周围的细胞类型特异性表观遗传调控的重要性。最新的遗传研究成果丰硕，因为在过去几年中发现了数十个 SLE 基因座，并且许多基因座已经通过整合 GWAS 信号与其他生物资源的系统方法得到了理解。在这篇综述中，我们总结了主要组织相容性复合体（MHC）和非 MHC 基因座中与 SLE 相关的遗传变异，检查了 SLE 的多基因风险评分及其与临床特征的关联。最后，描述了遗传关联下的变异驱动的发病功能，并讨论了 SLE 遗传研究中的挑战和未来方向。
