Causal association between frailty and arthritis: a bidirectional two-sample Mendelian randomization analysis

Abstract

Abstract Background Epidemiological data suggest close associations between frailty and osteoarthritis (OA) and rheumatoid arthritis (RA). However, whether these associations are causal is unclear. We therefore conducted a bidirectional Mendelian Randomization (MR) study to assess the causal relationship between frailty and OA and RA. Methods We extracted the summary genome-wide association statistics data of individuals of European ancestry for FI (N = 175266), OA (826690), and RA (58284). The two-sample MR analysis was primarily conducted using the inverse variance weighting method (IVW), followed by heterogeneity testing and sensitivity analysis. Results Genetically determined FI was significantly associated with an increased risk of all OA [odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.21 to 1.78, P < 0.001] and knee OA [OR = 1.78, 95% CI = 1.30 to 2.45, P < 0.001] but was not associated with hip OA [OR = 1.24, 95% CI = 0.97 to 1.59, P = 0.092] and RA [OR = 1.10, 95% CI = 0.73 to 1.66, P = 0.635]. In the reverse direction analysis, genetically determined all OA [beta = 0.22, 95% CI = 0.14 to 0.29, P < 0.001], hip OA [beta = 0.03, 95% CI = 0.01 to 0.05, P = 0.002], knee OA [beta = 0.10, 95% CI = 0.06 to 0.14, P < 0.001], and RA [beta = 0.03, 95% CI = 0.02 to 0.04, P < 0.001] showed significant associations with an increased risk of FI. The results were stable across sensitivity and validation analyses. Conclusion Our results indicate that frailty increases the risk of both all OA and knee OA but not hip OA and RA. In the reverse MR study, both OA and RA increased the risk of FI.