The causal relationship of asthma to sarcopenia revealed by Mendelian randomization analysis and meta-analysis

Abstract

Abstract Objectives: Sarcopenia is age-related muscle loss that results in low hand grip strength, loss of muscle weight and a slow walking speed. Asthma is recognized as a risk factor forsarcopenia. In this study, Mendelian randomization (MR) research was utilized to detect the causal impact and association of asthma and sarcopenia. Methods: A bidirectional two-sample MR analysis and a related meta-analysis were performed. To avoid the influence of sporadic factors, 3 asthma datasets were employed as exposures. Three datasets related to sarcopenia were used as outcomes. The inverse-variance weighted (IVW) method was set as the primary method,and other methods were set as auxiliary methods. Furthermore,these MR results were combined with those of a meta-analysis. The MR Egger method was employed to evaluate heterogeneity. Furthermore, a reverse-directional analysis was conducted to explore the causal impact of sarcopenia on asthma. Linkage disequilibrium score (LDSC) regression was utilized to explore genetic associations. Results: In the MR analysis of the relationship of asthma to sarcopenia, there was strong evidence of a causal effect of asthma on sarcopenia. The MR analysis of asthma to appendicular lean mass using the IVW method yielded a P value of 0.0047 when using the first dataset. The P value was 3.82E-06 for the second dataset and 1.32E-05 for the third. A P value of 0.0001 was obtained for the relationship of asthma to low hand grip strength using the IVW method with the first dataset, 4.08E-05 with the second and 2.86E-05 with the third. A Pvalue of 0.0425 was obtained for the relationship of asthma to walking speed using the IVW method with the first dataset, 4.23E-03 with the second and 4.23E-03 with the third. The meta-analysis combing 3 studies showed that there was a significant causal effect of asthma on appendicular lean mass (P<0.01), low hand grip strength (P<0.01), and walking speed (P<0.01). Reverse MR analysis suggested that sarcopenia exerted no causal effect onasthma. There was no pleiotropy in this MR study except for that in the reverse MR study. LDSC results suggested a weak genetic association. Conclusion: The MR study showed that asthma promotes the development of sarcopenia and is a significant risk factor forsarcopenia. However, a reverse causal effect does not exist.