Higher BMI might increase risk of ankle–foot sprains: A mendelian randomization study

Although previous research has suggested that a greater body mass index (BMI) may be linked to a higher incidence of ankle–foot sprains, the causal relationship between BMI and these injuries has not been established. This study aims to determine the causal effect of BMI-related features on ankle–foot sprains using a two-sample Mendelian randomization (MR) analysis.

Exposure single-nucleotide polymorphisms were collected from Genetic Investigation of Anthropometric Traits (GIANT Consortium) for BMI, hip circumference (HIP), hip circumference adjusted for BMI (HIP_adjBMI), waist circumference (WC), waist circumference adjusted for BMI (WC_adjBMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHR_adjBMI), encompassing a study population of more than 200​000 individuals. Furthermore, exposure statistics were gathered from MEC-IEU for body fat percentage (BFP), involving a study population of 454​633 individuals. Additionally, outcome statistics for ankle sprains were identified from FinnGen based on hospital discharge records (9141 cases and 290​508 healthy controls). Random-effect, inverse-variance weighted MR was used as the primary method.

BMI (β ​= ​0.173, p ​= ​0.035), BFP (β ​= ​0.341, p ​= ​9.08 ​× ​10⁻⁶), hip circumference (β ​= ​0.265, p ​= ​0.001), and WC (β ​= ​0.193, p ​= ​0.045) were found to have positive causal relationships with higher risk of ankle–foot sprains, whereas HIP_adjBMI, WC_adjBMI, WHR, and WHR_adjBMI were found to have no such effect. Additionally, no reverse causal effect was found between ankle–foot sprains and BMI or BFP.

A genetic predisposition to higher BMI-related features can lead to a higher risk of ankle–foot sprains, providing new insight into how to prevent ankle–foot sprains in middle-aged and elderly people.