Abstract
Previous studies have established associations between α-Klotho and frailty or sarcopenia; however, the causal nature of these relationships remains unclear. This study investigates the causal effects of α-Klotho on frailty and sarcopenia-related traits using Mendelian randomization (MR). Genetic instruments for circulating α-Klotho concentrations, frailty index (FI), low grip strength (LGS), appendicular lean mass (ALM), and walking pace were developed based on data from large genome-wide association studies. Two-sample MR analyses were performed, supplemented by sensitivity analyses to ensure the robustness of the findings. Reverse MR analyses were also conducted to explore potential reverse causation. The findings demonstrated an inverse causal relationship of circulating α-Klotho levels with FI (β = −0.020, 95% confidence interval [95% CI] = −0.036 to −0.004; p = 0.017) and LGS (β = −0.033, 95% CI = −0.061 to −0.004; p = 0.023). However, no causal relationship was observed between circulating α-Klotho levels and ALM or walking pace. Additionally, no evidence of reverse causation was identified between FI or sarcopenia-related traits and circulating α-Klotho levels. In conclusion, this MR analysis establishes an inverse causal relationship of circulating α-Klotho levels with both FI and LGS.
Get full access to this article
View all access options for this article.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
