Causal relationships between adiposity and childhood asthma: bi-directional Mendelian Randomization analysis

Background/objectives: Obesity and asthma are common chronic diseases and have been reported to be mutually causative. We investigated the causal direction of the relationship between adiposity and asthma using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Subjects/methods: We used data from the Taiwan Children Health Study with 24 body mass index (BMI)-single-nucleotide polymorphisms (SNPs, combined into a weighted allelic score) and 16 asthma-SNPs (combined into two weighted allelic scores, separately for asthma inflammatory and antioxidative genes) to yield genetic IVs for adiposity and asthma, respectively. Results: The weighted allele score for BMI was strongly associated with adiposity (p = 2 × 10^–16) and active asthma (p = 0.03). The two-stage least square regression risk ratio (RR) for the effect of BMI on asthma was 1.04 (95% confidence interval: 1.00–1.07, p = 0.03). Although the weighted asthma genetic scores were significantly associated with asthma (p = 8.4 × 10^–3), no association was seen for genetically instrumented asthma with BMI using MR. Central obesity was the most accurate predictor of asthma. Adiposity showed higher causal effects on asthma in boys and children with non-atopic asthma. Sensitivity analysis for MR revealed no directional genetic pleiotropy effects. The causal effect RRs of BMI on asthma were 1.04, 1.08, and 1.03 for inverse-variance weighted, MR–Egger regression (slope), and weighted median methods, respectively, all in accordance with the MR estimates. Conclusions: High adiposity may lead to asthma, whereas the effects of asthma on adiposity accumulation are likely to be small.