Observational, MR, and longitudinal association: mediators and
asthma
Both observational and MR studies supported the causal relationship
between mediators and asthma (Figure 3). High FEV1/FVC and physical
fitness reduced the risk of active asthma (OR, 0.98 and 0.93; 95% CI,
0.97–0.99 and 0.88–0.98, respectively), whereas SDB and early puberty
increased the risk of active asthma (OR, 1.03 and 1.22; 95% CI,
1.01–1.05 and 1.05–1.42, respectively). The IVW results of the MR
sensitivity analysis supported the findings of observational and MR
analyses (Figure E3). However, the results of the causal effect of
FeNO on asthma based on observational and MR analyses
were in the opposite direction, indicating that FeNO is
unlikely to mediate the association between obesity and asthma. The
prospective cohort analyses also demonstrated that higher FEV1/FVC and
physical fitness were associated with lower risk of active asthma
(RR<1), whereas early puberty increased the risk of active
asthma (RR>1) (Table 3).
The GRSs of the mediators served as an adequate indicator for the
mediators, except for the GRS of FeNO. The F statistics
for FEV1/FVC, FeNO, physical fitness, SDB, and early
puberty were 16.25, 3.22, 10.27, 19.93, and 88.54, respectively (Figure
3). Furthermore, the GRSs of all the mediators, except for
FeNO, were significantly associated with active asthma
(Table E2). We did not observe strong associations of the individual
SNPs of the mediators with active asthma (Tables E7–S11) and the
confounders (Tables E12–E16).