The association of appendicular lean mass and grip strength with LDL, VLDL and HDL particle diameter: a Mendelian randomization study of the UK Biobank cohort

Reduced muscle mass and strength is frequently associated with both alterations in blood lipids and poorer cardiometabolic outcomes in epidemiological studies; however, a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association of genetically determined appendicular lean mass (ALM) and handgrip strength (HGS) with serum lipid particle diameter. MR was implemented using summary-level data from the largest genome-wide association studies (GWAS) on ALM (n = 450,243), HGS (n = 223,315) and lipoprotein (LDL, VLDL and HDL) particle diameters (n = 115,078). Inverse variance weighted method (IVW) was used to calc ulate the causal estimates. Weighted median (WM)-based method, and MR-Egger, leave-one-out method were applied as sensitivity analysis. Greater ALM had a statistically significant positive effect on HDL particle diameter (MR-Egger: β=0.055, SE = 0.031, p = 0.081; IVW: β=0.068, SE = 0.014, p < 0.001), and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β= −0.114, SE = 0.039, p = 0.003; IVW: β= −0.081, SE = 0.017, p < 0.001). Similarly, greater HGS had a statistically significant positive effect on HDL particle diameter (MR-Egger: β=0.433, SE = 0.184, p = 0.019; IVW: β=0.121, SE = 0.052, p = 0.021), and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β=−0.416, SE = 0.163, p = 0.011; IVW: β=−0.122, SE = 0.046, p = 0.009). There was no statistically significant effect of either ALM or HGS on LDL particle diameter. There were potentially causal associations between both increasing ALM and HGS, and increasing HDL particle size and decreasing VLDL particle size. These causal associations may offer possibilities for interventions aimed at improving CVD risk profile.