Exploring the causal association between frailty index with the common types of arthritis: a Mendelian randomization analysis

Abstract Background Previous observational studies indicated a complex association between frailty and arthritis. Aims To investigate the genetic causal relationship between the frailty index and the risk of common arthritis. Methods We performed a large-scale Mendelian randomization (MR) analysis to assess frailty index associations with the risk of common arthritis in the UK Biobank (UKB), and the FinnGen Biobank. Summary genome-wide association statistics for frailty, as defined by the frailty index, and common arthritis including rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PSA), and ankylosing spondylitis (AS). The inverse-variance weight (IVW) method served as the primary MR analysis. Heterogeneity testing and sensitivity analysis were also conducted. Results Our results denoted a genetic association between the frailty index with an increased risk of OA, the odds ratio (OR) IVW in the UKB was 1.03 (95% confidence interval CI: 1.01–1.05; P = 0.007), and OR IVW was 1.55 (95% CI: 1.16–2.07; P = 0.003) in the FinnGen. For RA, the OR IVW from UKB and FinnGen were 1.03 (1.01–1.05, P = 0.006) and 4.57 (1.35–96.49; P = 0.025) respectively. For PSA, the frailty index was associated with PSA (OR IVW = 4.22 (1.21–14.67), P = 0.023) in FinnGen, not in UKB ( P > 0.05). However, no association was found between frailty index and AS ( P > 0.05). These results remained consistent across sensitivity assessments. Conclusion This study demonstrated a potential causal relationship that genetic predisposition to frailty index was associated with the risk of arthritis, especially RA, OA, and PSA, not but AS. Our findings enrich the existing body of knowledge on the subject matter.