Causal risk and protective factors for rheumatoid arthritis: a comprehensive mendelian randomization systematic review and meta-analysis
Abstract
Objective: To systematically synthesize Mendelian randomization (MR) evidence exploring causal associations between various exposures and rheumatoid arthritis (RA).
Methods: Systematic searches were conducted to identify eligible two-sample MR studies evaluating causal links between exposures and RA. Data extraction encompassed exposure types, genetic instruments, and analytical methods. The quality of evidence was evaluated based on STROBE-MR guidelines and evidence strength grades. Meta-analyses were performed using random-effects model with restricted maximum likelihood estimation and Hartung-Knapp-Sidik-Jonkman confidence intervals to summarize causal estimates.
Results: A total of 117 studies were included, comprising 496 MR associations across 248 unique exposures. Of these, 200 exposure-RA associations across 65 unique exposures were eligible for meta-analysis. The primary analysis identified smoking behavior (OR = 1.39, 95% CI 1.30-1.49) and hypothyroidism (OR = 1.55, 1.34-1.81) as significant risk factors with high-quality evidence. While television viewing (OR = 2.27, 1.77-2.90) and cholangitis (OR = 1.14, 1.06-1.23) showed nominal positive associations. Conversely, cognitive function (OR = 0.74, 0.68-0.81) and Interleukins-1 receptor antagonist (OR = 0.82, 95% CI 0.73-0.92) were identified as a nominally protective factor. In subtype analyses, basal metabolic rate emerged as a potential shared risk factor for both seropositive and seronegative RA. Overall, 7.66%…
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Evidence Hub reads this as a meta-analysis. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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