Mendelian Randomization Analysis
The random-effects inverse-variance weighted (IVW) method was used to estimate the bidirectional causality between childhood asthma and T1DM by meta-analyzing the SNP specific Wald ratio estimates.22 The causal effect estimates (beta coefficients) were transformed to odds ratios (OR). The weighted median, MR-Egger methods were also implemented to assess the causality.
Since many IVs are associated with multiple traits (pleiotropy), we used MR-Egger regression23 and MR pleiotropy residual sum and outlier (MR-PRESSO)24 method to examine the robustness of the main findings. When the MR-Egger intercept differs from zero (at P  < 0.05), horizontal pleiotropy or violation of the MR assumption is indicated.25MR-PRESSO method was used to correct the IVW-estimate via outlier removal, when MR-PRESSO outlier test suggested the presence of outlying variants. All MR analysis were performed using R version (4.0.3) with the “TwoSampleMR” and “MRPRESSO” package.26