Causal relationships of circulating Gal-3 levels to osteoarthritis risk: a Mendelian randomized study

Abstract

Background: Numerous animal and in vitro human chondrocyte studies have highlighted galectin-3 (Gal-3) as a risk factor for osteoarthritis (OA), but there is little supporting evidence from human studies. This study used Mendelian randomization (MR) to further explore the relationship between Gal-3 levels in human circulation and OA. Methods: Instrumental variables were obtained from published genome-wide association studies (GWASs). The OA data in the two samples Mendelian randomization (MR) came from the GWAS catalog database. The remaining data were obtained from the Integrative Epidemiology Unit (IEU) OpenGWAS database. Firstly, two-sample (MR) analysis was used to evaluate the association between Gal-3 levels and OA. Secondly, the causal relationship between circulating Gal-3 levels and obesity was studied using bidirectional two-sample MR. Thirdly, mediated MR was used to analyze whether the effect of circulating Gal-3 levels on the KOA predicted by genes was mediated by obesity. Results: Gal-3 levels were correlated with increased risk of KOA and HOA. Bidirectional MR analysis showed that a genetic predisposition to circulating Gal-3 levels was associated with increased risk of obesity, while a genetic predisposition to obesity was not associated with circulating Gal-3 levels. Mediated MR analysis suggested that waist circumference (WC) played a mediating role in the occurrence of KOA as a function of circulating Gal-3 levels. Conclusions: There is a causal relationship between Gal-3 levels and the occurrence of KOA and HOA, and its effect on KOA is mediated by WC to a certain extent.