Causal Associations of Obesity With Achilles Tendinopathy: A Two-Sample Mendelian Randomization Study.

Background: Achilles tendinopathy (AT) is associated with severe pain and is the cause of dysfunction and disability that are associated with significant reduction in social and economic benefits. Several potential risk factors have been proposed to be responsible for AT development; however, the results of observational epidemiological studies remain controversial, presumably because the designs of these studies are subject to residual confounding and reverse causality. Mendelian randomization (MR) can infer the causality between exposure and disease outcomes using genetic variants as instrumental variables, and identification of the causal risk factors for AT is beneficial for early intervention. Thus, we employed the MR strategy to evaluate the causal associations between previously reported risk factors (anthropometric parameters, lifestyle factors, blood biomarkers, and systemic diseases) and the risk of AT. Methods: Univariable MR was performed to screen for potential causal associations between the putative risk factors and AT. Bidirectional MR was used to infer reverse causality. Multivariable MR was conducted to investigate the body mass index (BMI)-independent causal effect of other obesity-related traits, such as the waist-hip ratio, on AT. Results: Univariable MR analyses with the inverse-variance weighted method indicated that the genetically predicted BMI was significantly associated with the risk of AT ( Conclusions: The causal association between BMI and AT risk suggests that weight control is a promising strategy for preventing AT and alleviating the corresponding disease burden.