A life course approach to elucidate the role of adiposity in asthma risk: evidence from a Mendelian randomisation study

Background Adiposity is associated with asthma although studies do not usually explore the inter-related role of childhood and adult adiposity in asthma risk using a life course perspective. Methods We conducted a Mendelian randomisation (MR) study using genetic instruments for childhood body mass index (BMI) (n=47 541), childhood obesity (n=29 822) and adult BMI (n=681 725) applied to the UK Biobank (n=401 837), with validation in a genome-wide association study of asthma (GABRIEL, n=5616). We used inverse variance weighting and other sensitivity analyses to examine the relationship between adiposity and asthma risk. We assessed mediation using multivariable Mendelian randomisation (MVMR) analysis. Results Childhood BMI was related to asthma in the UK Biobank (OR 1.10 per SD increase, 95% CI 0.99 to 1.22). Adult BMI was associated with asthma risk (OR 1.33 per SD increase, 95% CI 1.25 to 1.43). Analyses in GABRIEL gave directionally consistent results but with wide CI. The relationship between childhood obesity and asthma risk was less clear in both data sources. MVMR suggested the relation of childhood BMI with asthma risk was largely mediated via adult BMI. Conclusion Adiposity in childhood likely cause asthma, but the effect is primarily mediated via adult BMI.