Causal Relationship between Rheumatoid Arthritis and Atherosclerosis Risk: A Mendelian Randomized Study

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Abstract
Objectives Previous observational studies have revealed an association between rheumatoid arthritis (RA) and atherosclerosis (AS). However, observational studies are prone to bias due to potential confounding factors and reverse causality. Therefore, this study investigates the causal relationship between RA and AS risk using Mendelian randomization (MR). Methods Genetic data related to RA and AS were sourced from the Integrative Epidemiology Unit Open-Genome-Wide Association Studies database and the seventh edition of the FinnGen Biobank gene database, respectively. The initial analysis employed the inverse variance weighted (IVW) method for the MR analysis, with other methods utilized as supplementary methods. To ensure the robustness and reliability of the conclusions, various sensitivity analyses were conducted. Results The MR results indicate a positive causal relationship between genetically determined RA and the risk of coronary atherosclerosis(OR = 1.026, 95% CI: 1.004, 1.049, p = 0.179), peripheral atherosclerosis(OR = 1.072, 95% CI: 1.035, 1.111, p < 0.001), and atherosclerosis excluding coronary atherosclerosis, cerebral atherosclerosis, and PAD (ASE) (OR = 1.046, 95% CI: 1.015, 1.079, p = 0.004), while no significant causal relationship with cerebral AS was observed. The MR-Egger regression did not reveal any significant horizontal pleiotropy. Conclusion This study elucidates the causal relationship between RA and various AS risks, highlighting the importance of actively detecting and intervening in RA for AS risk.

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