Future risk of falls induced by ankle-foot sprains history: An observational and mendelian randomization study

Abstract

Background: Ankle-foot sprains are the most common musculoskeletal injuries, which can impair balance and theoretically increase the risk of falls, but still, there is a lack of evidence supporting the direct association between ankle-foot sprains and the future risk of falls.

Methods: UK Biobank cohort was utilized to measure the association between ankle-foot sprains and fall risk with covariates adjusted. Then, the two-sample Mendelian randomization (MR) analysis was applied based on the genetically predicated ankle-foot sprains from FinnGen to validate causal relationship. Finally, genetically predicated cerebellar neuroimaging features were used to explore the mediating role of maladaptive neuroplasticity between ankle-foot sprains and falls by two-step MR analyses.

Results: Patients with ankle-foot sprains history exhibited a slightly increased risk of falls than the matched controls before and after adjustment for covariates (odd ratio [OR] ranged from 1.632 to 1.658). Two-sample MR analysis showed that ankle-foot sprains led to a higher risk of falls (OR = 1.036) and a lower fractional anisotropy of superior cerebellar peduncle (SCP) (left, β = −0.052; right, β = −0.053). A trend of mediating effect was observed for the fractional anisotropy of right SCP in the causal effects of ankle-foot sprains on falls (β = 0.003).

Conclusion: The history of ankle-foot sprains is associated with a slightly increased risk of falls. These findings improve our understanding of the clinical consequences of ankle-foot sprains in terms of fall risk and suggest the importance of adopting more efficient strategies for managing residual functional deficits after the injuries.

Keywords

Leg injuries / Accidental falls / Postural balance / Mendelian randomization analysis / UK biobank / FinnGen

Ethical approval statement

All analyses were performed on publicly available individual-level data and summary-level GWAS statistics from the UK biobank (http://www.ukbiobank.ac.uk/) and FinnGen (https://www.finngen.fi/fi) database. Ethics approval was obtained from respective institutional review boards and participants' informed consent was provided in these cohort projects.

Funding

This work was supported by the National Natural Science Foundation of China [No. 81871823, 81971583, 81671652, 8207090113], National Key R&D Program of China [No. 2018YFC1312900], Natural Science Foundation of Shanghai [No. 20ZR1406400], Science and Technology Commission of Shanghai Municipality [No. 18JC1410403], Shanghai Municipal Science and Technology Major Project [No.2017SHZDZX01, 2018SHZDZX01], and Shanghai Science and Technology Committee [No. 22dz1204700].

Data statement

All data are publicly available, and the codes are available upon reasonable request corresponding to the authors.

CRediT authorship contribution statement

Xiao'ao Xue: Conceptualization, Formal analysis, Writing - original draft, Methodology. Weichu Tao: Conceptualization, Formal analysis, Writing - original draft, Methodology. Qianru Li: Conceptualization, Formal analysis, Methodology, Writing - original draft. Yi Li: Data curation, Methodology, Writing - review & editing. Yiran Wang: Data curation, Methodology, Writing - review & editing. Le Yu: Software, Visualization, Writing - review & editing. Xicheng Gu: Software, Visualization, Writing - review & editing. Tian Xia: Data curation, Resources, Writing - review & editing. Rong Lu: Data curation, Resources, Writing - review & editing. Ru Wang: Funding acquisition, Project administration, Supervision, Writing - review & editing. He Wang: Funding acquisition, Project administration, Supervision, Writing - review & editing. Yinghui Hua: Conceptualization, Funding acquisition, Supervision, Writing - review & editing.

Declaration of competing interest

The authors have no direct or indirect interests that are in direct conflict with the conduction of this study.

Acknowledgements

The authors would like to express their gratitude to EditSprings (https://www.editsprings.cn) for the expert linguistic services provided, and Dr. Aichen Xia from Shanghai Jiao Tong University for the help of downloading GWAS data.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.smhs.2024.05.002https://doi.org/10.1016/j.smhs.2024.05.002.

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