Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
Ann Rheum Dis. 2021 Jun;80(6):689-697. doi: 10.1136/annrheumdis-2019-216794. Epub 2021 Jan 6.
For more than a decade, genome-wide association studies have been applied to autoimmune diseases and have expanded our understanding on the pathogeneses. Genetic risk factors associated with diseases and traits are essentially causative. However, elucidation of the biological mechanism of disease from genetic factors is challenging. In fact, it is difficult to identify the causal variant among multiple variants located on the same haplotype or linkage disequilibrium block and thus the responsible biological genes remain elusive. Recently, multiple studies have revealed that the majority of risk variants locate in the non-coding region of the genome and they are the most likely to regulate gene expression such as quantitative trait loci. Enhancer, promoter and long non-coding RNA appear to be the main target mechanisms of the risk variants. In this review, we discuss functional genetics to challenge these puzzles.
十多年来，全基因组关联研究已应用于自身免疫性疾病，并扩展了我们对发病机制的认识。与疾病和特征相关的遗传风险因素本质上是致病的。然而，从遗传因素阐明疾病的生物学机制具有挑战性。事实上，在同一单倍型或连锁不平衡块上定位的多个变体中确定因果变体是很困难的，因此负责的生物基因仍然难以捉摸。最近，多项研究表明，大多数风险变体位于基因组的非编码区域，它们最有可能调节基因表达，如数量性状位点。增强子、启动子和长非编码 RNA 似乎是风险变体的主要作用机制。在这篇综述中，我们讨论了功能遗传学来挑战这些难题。
