Sharma Seema D, Leung Shek H, Viatte Sebastien
Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK; NIHR Manchester Musculoskeletal Biomedical Research Centre, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
Best Pract Res Clin Rheumatol. 2024 Dec;38(4):101968. doi: 10.1016/j.berh.2024.101968. Epub 2024 Jul 2.
In the past four decades, a plethora of genetic association studies have been carried out in cohorts of patients with rheumatoid arthritis. These studies have highlighted key aspects of disease pathogenesis and suggested causal mechanisms. In this review, we discuss major advances in our understanding of the genetic architecture of rheumatoid arthritis susceptibility, severity and treatment response and explain how genetics supports current models of disease pathogenesis and outcome. We outline future research directions, like Mendelian randomisation, and present a number of potential avenues for clinical translation, including risk and outcome prediction, patient stratification into treatment response groups and pharmacological applications.
在过去的四十年里,针对类风湿性关节炎患者队列开展了大量的基因关联研究。这些研究突出了疾病发病机制的关键方面,并提出了因果机制。在本综述中,我们讨论了在理解类风湿性关节炎易感性、严重程度和治疗反应的遗传结构方面取得的主要进展,并解释了遗传学如何支持当前的疾病发病机制和预后模型。我们概述了未来的研究方向,如孟德尔随机化,并提出了一些临床转化的潜在途径,包括风险和预后预测、将患者分层为治疗反应组以及药物应用。