Observational and MR association: obesity and asthma
Our previous bidirectional MR analysis established that adiposity causes asthma, but that asthma does not lead to adiposity accumulation.2 In the current study, we confirmed the causal direction from obesity to asthma using TCHS cohorts 1 and 2 (Figure E1). A one-unit increase in z-BMI was associated with an elevated risk of active asthma according to both observational analysis (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.04–1.28) and MR 2SLS analysis (OR, 1.07; 95% CI, 1.00–1.14). In addition, the sensitivity analysis also yielded evidence of a positive causal relationship between z-BMI and asthma.
The GRSs of the 28 BMI-SNPs were robustly correlated with z-BMI (Table E1, F-statistics = 44.41, p < 0.001) and were associated with active asthma (Table E1, p = 0.04). To prove that the individual SNP used was independent of asthma and confounders, we showed that most of the 28 BMI-SNPs were associated with z-BMI (Table E3), but that there was little evidence to support an association between individual BMI-SNPs and active asthma and confounders (Tables E3 and E4).