AUTHOR=Jia Xue-Min , Deng Ting-Ting , Su Hang , Shi Hao-Jun , Qin Hao , Yu Gong-Chang , Yin Ying , Liu Fan-Jie , Shi Bin 

TITLE=Genetic causality and site-specific relationship between sarcopenia and osteoarthritis: a bidirectional Mendelian randomization study

JOURNAL=Frontiers in Genetics

VOLUME=Volume 14 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1340245

DOI=10.3389/fgene.2023.1340245

ISSN=1664-8021

ABSTRACT=Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA.We used pooled genetic data from the UK Biobank for ALM(n=450,243), left-hand grip strength (n= 461,026), right-hand grip strength(n=461,089) and usual walking pace(n=459,915).Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA(n=826,690), hand OA(n=303,7782), hip OA(n=353,388) and knee OA(n=396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted P values (PFDR). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses.We discovered ALM (odds ratio (OR) =1.103, 95% confidence interval (CI) =1.052-1.156, PFDR = 2.87E-04), hand grip strength (left, IVW OR=0.823, 95% CI = 0.712 to 0.952, PFDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, PFDR =0.020), and usual walking pace (OR= 0.339, 95% CI = 0.204 to 0.564, PFDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (β = -0.258, 95% CI = -0.369 to 0.146, PFDR = 0. 6.07E-06), grip strength (left, β = -0.064, 95% CI = -0.104 to 0.024, PFDR = 0.002; right, β = -0.055, 95% CI = -0.095 to 0.014, PFDR = 0.008), and usual walking pace (β=-0.104, 95% CI = -0.147 to 0.061, PFDR = 1.61E-05).Conclusions: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP.