Abstract
BACKGROUND: Evidence from observational epidemiological studies indicated that rheumatoid arthritis (RA) increased the risk of heart failure (HF). However, there is a possibility that the correlation is not explained as a causative role for RA in the pathogenesis of HF. A two-sample Mendelian randomization (MR) framework was designed to explore the potential etiological role of RA in HF to identify the target to improve the burden of HF disease. METHODS: To assess the causal association between RA and HF, we analyzed summary statistics from genome-wide association studies (GWASs) for individuals of European descent. Genetic instruments for RA were identified at a genome-wide significance threshold (p < 5 × 10(-8)). Corresponding data were obtained from a GWAS meta-analysis (95,524 cases and 1,270,968 controls) to identify genetic variants underlying HF. MR estimates were pooled using the inverse variance weighted method. Complementary analyses were conducted to assess the robustness of the results. RESULTS: There was no evidence of a causal association between genetically predicted RA and HF [odds ratio (OR), 1.00; 95% confidence interval (CI), 0.99-1.02; P = 0.60]. Various sensitivity analyses suggested no pleiotropy detected (all p > 0.05). CONCLUSION: Our findings did not support the causal role of RA in the etiology of HF. As such, therapeutics targeted at the control of RA may have a lower likelihood of effectively controlling the occurrence of HF.