3.1 MR results of asthma in 3 characteristic sarcopenia datasets
As shown in Figure. 1A, a P value of 0.0047 < 0.05 was obtained via MR analysis of the relationship of asthma to appendicular lean mass using the IVW method using asthma dataset 1, a P value of 3.82E-06 was obtained using dataset 2, and a P value of 1.32E-05 was obtained using dataset 3. The combined effect of asthma on appendicular lean mass was also revealed by the meta-analysis, as indicated in Figure. 1B. The obtained value of P < 0.01 indicated that asthma had a significant causal association with appendicular lean mass.
As shown in Figure. 1C, MR analysis of asthma with low hand grip strength using the IVW method revealed P values of 0.0001 < 0.05 for asthma dataset 1, 4.08E-05 for dataset 2, and 2.86E-05 for dataset 3. The combined effect of asthma on appendicular lean mass was observed in the meta-analysis, as indicated in Figure. 1D. The P value of the meta-analysis was also < 0.01, indicating that asthma had a significant causal association with low hand grip strength.
As shown in Figure. 1E, the MR analysis results of the relationship of asthma to walking speed using the IVW method yielded P values of 0.0425 < 0.05 with asthma dataset 1, 4.23E-03 with dataset 2, and 4.23E-03 with dataset 3. The combined effect of asthma on appendicular lean mass was similarly shown by the meta-analysis, as indicated in Figure. 1F, with P < 0.01, indicating that asthma had a significant causal association with walking speed.
3.2 Effect of asthma on 3 characteristic sarcopenia datasets
As shown in Figure. 2A, MR results using the first asthma dataset showed that appendicular lean mass decreased with increasing severity of asthma; this finding was visualized in the scatter plot showing the 5 methods. Similar tendencies were observed, shown in Figure. 2B and Figure. 2C, using asthma dataset 2 and asthma dataset 3. These analyses demonstrated that asthma decreases appendicular lean mass.
As shown in Figure. 2D, MR results using the first asthma dataset showed that low grip strength increased with increasing severity of asthma; this finding was visualized in in the scatter plot showing the 5 methods. Similar tendencies were observed, shown in Figure. 2E and Figure. 2F, using asthma dataset 2 and asthma dataset 3. These analyses suggested that asthma increases the occurrence of low grip strength.
As shown in Figure. 3A, MR results using the first asthma dataset showed that the walking speed decreased with increasing severity of asthma; this finding was visualized in in the scatter plot showing the 5 methods. Similar tendencies were observed, shown in Figure. 3B and Figure. 3C, using asthma dataset 2 and asthma dataset 3. These analyses demonstrated that asthma decreases walking speed.
3.3 Reverse MR analysis of sarcopenia to asthma
Interestingly, all the obtained P values were > 0.05 following the MR analysis of the appendicular lean mass to assess its relationship to 3 asthma datasets when using the IVW method as well as the other 4 auxiliary methods, as shown in Figure. 4A. all the obtained P values were > 0.05 when the low hand grip strength to 3 asthma datasets which indicated in Figure. 4B while the walking speed to 3 asthma datasets in Figure. 4C. These results reliably suggested that sarcopenia had no significant causal effect on asthma.
3.4 Sensitivity analysis
As shown in Figure. 5A-5F and Figure. 6A-6C, the data were roughly equally distributed on both sides, indicating that there was no bias in the data. Following the heterogeneity and horizontal pleiotropy tests, the P values reflecting the heterogeneity of data (including that obtained via MR‒Egger and IVW methods) were greater than 0.05, as shown in Table. 2. The intercepts of the MR‒Egger regression method were close to 0 in most MR analyses except a reverse MR analysis of asthma 1 dataset to walk pace. The sensitivity analyses using LOO analysis (Supplementary 1 to Supplementary 6) to investigate stability revealed no sensitivity to the results. For the LOO analysis, all results using a single SNP removal were stable on the same side of 0, suggesting stable results in all conventional and reverse MR analyses.
3.5 Evaluation of genetic correlation
LDSC-based estimates showed a marginal genetic correlation between appendicular lean mass data and the information from the first asthma dataset (Rg = -0.6198, Se = 0.3726, P = 0.0962), second asthma dataset (Rg = -0.5621, Se = 0.5661, P = 0.3207), and third asthma dataset (Rg = -0.5021, Se = 0.3464, P = 0.1472). Low hand grip strength had no correlation for the first asthma dataset (Rg = 0.1008, Se = 0.2859, P = 0.7244), second asthma dataset (Rg = 0.0541, Se = 0.6478, P = 0.9334), and third asthma dataset (Rg = 0.1474, Se = 0.3400, P = 0.6646). Walking speed showed a correlation for the first asthma dataset (Rg =-1.4659, Se = 0.3802, P = 0.0001), second asthma dataset (Rg = -0.9115, Se = 0.1820, P = 5.48E-07), and third asthma dataset (Rg =-0.5106, Se = 0.0893, P = 1.08E-08). The values of P > 0.05 obtained from LDSC statistical analysis except for that corresponding to the relationship of walking speed to the 3 asthma datasets suggested that MR estimates are not confounded by shared genetic components.