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ORIGINAL RESEARCH article

Front. Med.
Sec. Rheumatology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1405188
This article is part of the Research Topic Advances in Chronic Pain Treatment View all 9 articles

Causal relationship between modifiable risk factors and knee osteoarthritis: A Mendelian randomization study

Provisionally accepted
Zhihao Diao Zhihao Diao 1Danyang Guo Danyang Guo 1*Jingzhi Zhang Jingzhi Zhang 1*Ruiyu Zhang Ruiyu Zhang 1*Chunjing Li Chunjing Li 1*Hao Chen Hao Chen 2*Yuxia Ma Yuxia Ma 1*
  • 1 Shandong University of Traditional Chinese Medicine, Jinan, China
  • 2 Complutense University of Madrid, Madrid, Madrid, Spain

The final, formatted version of the article will be published soon.

    Background: While several risk factors for knee osteoarthritis (KOA) have been recognised, the pathogenesis of KOA and the causal relationship between modifiable risk factors and KOA in genetic epidemiology remain unclear. This study aimed to determine the causal relationship between KOA and its risk factors. Methods: Data were obtained from published Genome-Wide Association study (GWAS) databases. A two-sample mendelian randomization (MR) analysis was performed with genetic variants associated with risk factors as instrumental variables and KOA as outcome. First, inverse variance weighting was used as the main MR analysis method, and then a series of sensitivity analyses were conducted to comprehensively evaluate the causal relationship between them. Results: Univariate forward MR analysis revealed that genetically predicted hypothyroidism, hyperthyroidism/thyrotoxicosis, educational level, income level, metabolic syndrome (MS), essential hypertension, height, hot drink temperature, diet (abstaining from sugar-sweetened or wheat products), and psychological and psychiatric disorders (stress, depression, and anxiety) were causally associated with KOA. Reverse MR exhibits a causal association between KOA and educational attainment. Multivariate MR analysis adjusted for the inclusion of potential mediators, such as body mass index (BMI), smoking, alcohol consumption, and sex, exhibited some variation in causal effects. However, hyperthyroidism/thyrotoxicosis had a significant causal effect on KOA, and there was good evidence that height, hypothyroidism, educational level, psychological and psychiatric disorders (stress, depression, and anxiety), and abstaining from wheat products had an independent causal relationship. The mediating effect of BMI as a mediator was also identified. Conclusion: This study used MR to validate the causal relationship between KOA and its risk factors, providing new insights for preventing and treating KOA in clinical practice and for developing public health policies.

    Keywords: Mendelian randomization, knee osteoarthritis, Risk factors, causal relationship, genetic variants

    Received: 22 Mar 2024; Accepted: 28 May 2024.

    Copyright: © 2024 Diao, Guo, Zhang, Zhang, Li, Chen and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Danyang Guo, Shandong University of Traditional Chinese Medicine, Jinan, China
    Jingzhi Zhang, Shandong University of Traditional Chinese Medicine, Jinan, China
    Ruiyu Zhang, Shandong University of Traditional Chinese Medicine, Jinan, China
    Chunjing Li, Shandong University of Traditional Chinese Medicine, Jinan, China
    Hao Chen, Complutense University of Madrid, Madrid, 28040, Madrid, Spain
    Yuxia Ma, Shandong University of Traditional Chinese Medicine, Jinan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.