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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

Kirwan, R, Mazidi, M, Butler, T, Perez de Heredia, FP, Lip, GYH and Davies, IG (2024) 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. European Heart Journal Open.

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Abstract

Background and aims 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. Methods 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. Results 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. Conclusions 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.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions: Biological & Environmental Sciences (from Sep 19)
Nursing & Allied Health
Sport & Exercise Sciences
Publisher: Oxford University Press
SWORD Depositor: A Symplectic
Date Deposited: 20 Mar 2024 13:55
Last Modified: 02 Apr 2024 15:39
DOI or ID number: 10.1093/ehjopen/oeae019
Editors: Larsson, SC
URI: https://researchonline.ljmu.ac.uk/id/eprint/22868
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