Causal Associations between frailty and low back pain: a bidirectional two-sample Mendelian randomization study

Abstract Background Previous observational studies have revealed a potentially robust reciprocal bidirectional relationship between frailty and low back pain (LBP). However, the precise causal relationship remains unclear. Methods To examine the potential causal association between frailty and low back pain, we conducted bidirectional two-sample Mendelian randomization analysis (MR) study. Genetic data on frailty index (FI) and LBP were acquired from publicly available genome-wide association studies (GWAS). Various MR methodologies were utilized, such as random effects inverse variance weighting (IVW), weighted median, and MR-Egger, to evaluate causality. Additionally, sensitivity analyses were conducted to evaluate the robustness of the findings. Results Genetically predicted higher frailty index (IVW, odds ratio [OR] = 1.66, 95% CI 1.17–2.36, p = 4.92E-03) was associated with a higher risk of low back pain. As for the reverse direction, genetic liability to low back pain showed consistent associations with a higher frailty index (IVW, OR = 1.13, 95% CI 1.07–1.19, p = 2.68E-05). The outcomes from various MR techniques and sensitivity analyses indicate the robustness of our findings. Conclusion Our research findings provide additional evidence bolstering the bidirectional causal relationship between frailty and LBP.