A lifecourse Mendelian randomization study uncovers age-dependent effects of adiposity on asthma risk

Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n = 13,962 cases) and adult-onset asthma (n = 26,582 cases) with a common set of controls (n = 300,671) using a technique known as lifecourse Mendelian randomization. We found that childhood adiposity directly increases risk of pediatric asthma (OR = 1.20, 95% CI = 1.03–1.37, p = 0.03), but limited evidence that it has an effect on adult-onset asthma after accounting for adiposity during adulthood (OR = 1.05, 95% CI = 0.93–1.17, p = 0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife (OR = 1.37, 95% CI = 1.28–1.46, P = 7 × 10(−12)). These findings suggest that childhood and adulthood adiposity are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse.