2.3 IVs selection criteria
SNPs associated with the exposures at genome-wide significance (P < 5.0×10-8) were selected as IVs. However, this criterion was too strict for mixed asthma: only one SNP could be used as the IV, so we set a P value of less than 5.0×10-6 for mixed asthma only. Then, independent IVs were identified utilizing the cutoff of the matching linkage disequilibrium (LD) value (threshold set at r2 < 0.001 and clump window > 10,000 kb) to ensure their independence. We further removed SNPs associated with the outcomes (P<5.0×10-5) and SNPs associated with confounders via the PhenoScannerV2 database (http://www.phenoscanner.medschl.cam.ac.uk/). To assess the strength of IVs, the F statistic was calculated for each IV: F statistic = R2 (N-2)/(1-R2), R2: the phenotypic variance explained by each IV in the exposure, N: the sample size14,15. IVs with an F statistic < 10 were considered weak and should be deleted16.