An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study

Background As a geriatric syndrome, sarcopenia has a high prevalence in the old population and represents an impaired state of health with adverse health outcomes. A strong clinical interest in its relationship with venous thromboembolism (VTE), which is a complex trait disease with a heterogeneous annual incidence rate in different countries, has emerged. The relationship between sarcopenia and venous thromboembolism has been reported in observational studies but the causality from sarcopenia to VTE remained unclarified. We aimed to assess the causal effect of sarcopenia on the risk of VTE with the two-sample Mendelian randomization (MR) method. Methods Two sets of single-nucleotide polymorphisms (SNPs), derived from two published genome-wide association study (GWAS) meta-analyses and genetically indexing muscle weakness and lean muscle mass separately, were pooled into inverse variance weighted (IVW), weighted median and MR-Egger analyses. Results No evidence was found for the causal effect of genetically predicted muscle weakness (IVW: OR = 0.90, 95% CI = 0.76–1.06, p = 0.217), whole body lean mass (IVW: OR = 1.01, 95% CI = 0.87–1.17, p = 0.881) and appendicular lean mass (IVW: OR = 1.13, 95% CI = 0.82–1.57, p = 0.445) on the risk of VTE. However, both genetically predicted whole-body lean mass and appendicular lean mass can causally influence diabetes mellitus (IVW of whole-body lean mass: OR = 0.87, 95% CI = 0.78–0.96, p = 0.008; IVW of appendicular lean mass: OR = 0.71, 95% CI = 0.54–0.94, p = 0.014) and hypertension (IVW of whole-body lean mass: OR = 0.92, 95% CI = 0.87–0.98, p = 0.007; IVW of appendicular lean mass: OR = 0.84, 95% CI = 0.73–0.96, p = 0.013). Conclusions Genetically predicted sarcopenia does not causally influence VTE directly, but it might still have an indirect effect on VTE incidence via diabetes mellitus and hypertension.