Zhang Jie, Zhou Chun, Guan Shaoxing
Department of Pharmacy, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, China.
Twin Res Hum Genet. 2024 Jun;27(3):169-173. doi: 10.1017/thg.2024.24. Epub 2024 Jun 3.
Immunity activation and inflammation are the main characteristics of rheumatoid arthritis and clonal hematopoiesis. However, it remains unclear whether rheumatoid arthritis increase the risk of clonal hematopoiesis. Here, a Mendelian randomization (MR) analysis was conduct to explore the causal effects of rheumatoid arthritis on clonal hematopoiesis. Summary statistics data of rheumatoid arthritis (13,838 cases and 33,742 controls) and clonal hematopoiesis (10,203 cases and 173,918 controls) derived from a genomewide association study were selected to analyze. We selected inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode to evaluate the causal effect of rheumatoid arthritis on clonal hematopoiesis. The two-sample MR analysis suggested a strong causal relationship between rheumatoid arthritis and clonal hematopoiesis by inverse-variance weighted ( = 1.002311673, 95% CI [1.000110757, 1.004517433], = .039706) and weighted median ( = 1.002311673, 95% CI [1.000110757, 1.004517433], = .039518447) methods. No significant pleiotropy or heterogeneity was found in the sensitivity analysis. These results supported a potentially causal relationship between rheumatoid arthritis and clonal hematopoiesis, and the exposure of rheumatoid arthritis increased the risks of clonal hematopoiesis. Our findings highlight the importance of how chronic inflammation and immune activation induced rheumatoid arthritis enhances the risks of clonal hematopoiesis, and that early intervention with rheumatoid arthritis patients might reduce the clonal hematopoiesis risks in rheumatoid arthritis patients. Moreover, our study provides clues for prediction of risk factors and potential mechanisms of clonal hematopoiesis.
免疫激活和炎症是类风湿性关节炎和克隆性造血的主要特征。然而，类风湿性关节炎是否会增加克隆性造血的风险仍不清楚。在此，进行了一项孟德尔随机化（MR）分析，以探讨类风湿性关节炎对克隆性造血的因果效应。选择了来自全基因组关联研究的类风湿性关节炎（13838例病例和33742例对照）和克隆性造血（10203例病例和173918例对照）的汇总统计数据进行分析。我们选择了逆方差加权法、MR-Egger法、加权中位数法、简单模式法和加权模式法来评估类风湿性关节炎对克隆性造血的因果效应。两样本MR分析表明，通过逆方差加权法（β = 1.002311673，95%CI [1.000110757，1.004517433]，P = 0.039706）和加权中位数法（β = 1.002311673，95%CI [1.000110757，1.004517433]，P = 0.039518447），类风湿性关节炎与克隆性造血之间存在很强的因果关系。在敏感性分析中未发现显著的多效性或异质性。这些结果支持了类风湿性关节炎与克隆性造血之间潜在的因果关系，类风湿性关节炎的暴露增加了克隆性造血的风险。我们的研究结果突出了类风湿性关节炎所诱导的慢性炎症和免疫激活如何增加克隆性造血风险的重要性，以及对类风湿性关节炎患者进行早期干预可能会降低其克隆性造血风险。此外，我们的研究为克隆性造血的危险因素预测和潜在机制提供了线索。
