A Bidirectional Mendelian Randomization Study of Sarcopenia-Related Traits and Knee Osteoarthritis

Abstract

Background: With the development of population aging worldwide, sarcopenia and knee osteoarthritis (KOA), two age-related diseases, will continue to impose increasing medical and economic burdens on the society. Previous studies have discovered an association between the two, but the causality remains controversial, and it is difficult to eliminate confounding factors. Therefore, a Mendelian randomization (MR) study was conducted to overcome these confounding factors and investigate the causal relationship between sarcopenia and KOA. Objective: The present work focused on assessing the causality between KOA and sarcopenia, so as to provide new strategies to prevent and treat these two conditions in clinic. Methods: We registered the title with PROSPERO (ID: CRD42023421096). The two-sample bidirectional MR analysis was conducted in two steps, with sarcopenia being the exposure whereas KOA being the outcome in the first step, and vice versa in the second step. Genomewide association studies (GWAS) data on low hand-grip strength (n=256,523), walking pace (n=459,915), appendicular lean mass (ALM, n=450,243), and KOA (n=403,124) were obtained from the UK Biobank. Methods such as the inverse variance weighted (IVW) and weighted median were utilized for assessing the causality of KOA with sarcopenia, and sensitivity analyses were also conducted. Results: In the main MR analysis using the IVW method, evidence suggested that low hand-grip strength, walking pace, and ALM had adverse effects on KOA (p-value 0.0001, odds ratio (OR) 1.4569, 95% confidence interval (CI) 1.2007-1.7677 for low hand-grip strength; p-value 0.0003, OR 1.1500, 95% CI 1.050-1.183 for ALM; p-value 5.29E-19, OR 0.0932, 95% CI 0.0553-0.1572 for walking pace). However, there was no causality of KOA with sarcopenia in the opposite direction. Conclusion: Our study suggests an obvious unidirectional causality of KOA with sarcopenia, and supports the notion that patients with sarcopenia are more susceptible to the development of KOA.

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study

“…The relationship between sarcopenia and arthritis has drawn increasing attention. Previous MR studies on sarcopenia and osteoarthritis mainly employed UVMR analysis [ 42 – 44 ], and they found a positive causal relationship between ALM and KOA, as well as HOA, and a negative causal relationship between UWP and KOA, as well as HOA, consistent with the findings of this study. Furthermore, the causal relationship between LHG and KOA was also found in the UVMR analysis of the present study.…”

Evidence for Genetic Causal Relationships Between Multiple Immune-Mediated Inflammatory Diseases and Age-Related Macular Degeneration: A Univariable and Multivariable Mendelian Randomization Study

“…In this study, a two-sample MR analysis method was employed, and then instrumental variables (IVs) were obtained for various IMIDs based on public summary data. The method contributes to the effective addressing of confounding bias present in conventional epidemiological studies and to investigating the causal relationship between these diseases and AMD [ 20 ]. Three assumptions must be satisfied to consider a genetic variant as a valid IV for MR analysis: The variant is associated with the exposure.…”

The causal relationship of asthma to sarcopenia revealed by Mendelian randomization analysis and meta-analysis

“…Three asthma datasets were employed as exposures. It is commonly acknowledged that the following three datasets are used as feature datasets for sarcopenia, which containing information about appendicular lean mass, low hand grip strength and walking speed were employed as outcomes of sarcopenia, following the guidance of previously MR analyses of sarcopenia [17,21].…”