Investigating the causal relationship between physical activity and chronic back pain: a bidirectional two-sample Mendelian randomization study

BackgroundRecent observational studies have reported a negative association between physical activity and chronic back pain (CBP), but the causality of the association remains unknown. We introduce bidirectional Mendelian randomization (MR) to assess potential causal inference between physical activity and CBP. MethodsThe two-sample MR was used with independent genetic variants associated with physical activity phenotypes and CBP as genetic instruments from large genome-wide association studies (GWASs) on individuals of European ancestry. The effects of both directions (physical activity to CBP and CBP to physical activity) were examined. Inverse variance-weighted meta-analysis and alternate methods (weighted median and MR-Egger) were used to combine the MR estimates of the genetic instruments. Multiple sensitivity analyses were conducted to examine the robustness of the results. ResultsFor primary analysis, instrumental variables were extracted from 337,234 participants for physical activity (the same as the outcome cohort) and 158,025 participants (29,531 cases) for CBP, while the outcome cohort for CBP included 117,404 participants (80,588 cases). No evidence of a causal relationship was found in the direction of physical activity to CBP (odds ratio [OR], 0.98; 95% CI, 0.85-1.13; P = 0.81). In contrast, a negative causal relationship in the direction of CBP to physical activity was detected ({beta} = -0.07; 95% CI, -0.12 to -0.01; P = 0.02), implying a reduction in moderate-vigorous physical activity (approximately 146 MET-minutes/week) for participants with CBP relative to controls. ConclusionsThe negative relationship between physical activity and CBP is probably derived from the reduced physical activity of patients experiencing CBP rather than the protective effect of physical activity on CBP. Highlights[tpltrtarr] Previous studies found a negative relationship between physical activity and chronic back pain, but the causal inference behind the relationship is lacking in evidences. [tpltrtarr]We applied Mendelian randomization and revealed that the negative relationship probably derived from the fact that patients experiencing CBP tend to reduce their physical activities. [tpltrtarr]If the negative relationship between physical activity and CBP is truly a reverse causality, the concept that patients with CBP should be engaging in activity, which is recommended by current guidelines, may need to be reconsidered.