The causal effect of sarcopenia-associated traits on brain cortical structure: A Mendelian randomization study

Previous observational studies have reported sarcopenia can affect the structure and function of brain cortical structure. However, the causality inferred from those studies was subjected to residual confounding and reverse causation. Herein, we use a two-sample Mendelian randomization (MR) analysis to illustrate the causal effect of sarcopenia-associated traits on brain cortical structure.

We selected appendicular lean mass (ALM), hand grip strength (left and right) (HGSL and HGSR), and usual walking pace (UWP) to symbolize sarcopenia. The definition of brain cortical structure is human brain cortical surface area (SA) and cortical thickness (TH) globally and in 34 functional regions measured by magnetic resonance imaging. Instrumental variables at the genome-wide significance level were obtained from publicly available datasets, and inverse variance weighted as the primary method was used for MR analysis.

At the global level, we found ALM (β=2604.68, 95 % confidence interval (CI): 1886.17 to 3323.19, P = 1.20 × 10^-12) and HGSR (β=4733.05, 95 % CI: 2245.08 to 7221.01, P = 1.93 × 10^-4) were associated with increased SA. At the region level, the SA of 25 functional gyrus without global weighted was influenced by ALM. The HGSR significantly increased SA of medial orbitofrontal and precentral gyrus without global weighted and ALM was associated with decrease of TH of lateral occipital gyrus with global weighted. No pleiotropy was detected.

This was the first MR study investigated the causal effect of sarcopenia-associated traits on brain cortical structure. In our study, we revealed genetically predicted sarcopenia-associated traits including ALM and HGSR could affect brain cortical structure.