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Association Between Rheumatoid Arthritis and Clonal Hematopoiesis: A Mendelian Randomization Study

Published online by Cambridge University Press:  03 June 2024

Jie Zhang ,
Chun Zhou  and
Shaoxing Guan Open the ORCID record for Shaoxing Guan [Opens in a new window]
Jie Zhang
Affiliation:
Department of Pharmacy, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
Chun Zhou
Affiliation:
School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, China
Shaoxing Guan*
Affiliation:
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
*
Corresponding author: Shaoxing Guan; Email: Guanshx6@mail.sysu.edu.cn
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Abstract

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 (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .039706) and weighted median (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .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.

Keywords

Rheumatoid arthritisClonal hematopoiesisMendelian randomization
Type
Article
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Twin Research and Human Genetics , First View , pp. 1 - 5
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Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of International Society for Twin Studies

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