Age-dependent effects of adiposity on asthma risk during childhood and adulthood: a lifecourse Mendelian randomization study

BackgroundSeparating the direct and 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. MethodsIn 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. FindingsWe found that childhood adiposity increases risk of pediatric asthma (OR=1.20, 95% CI=1.03 to 1.37, P=0.03), whereas there was weak evidence that it has a long-term influence on adult-onset asthma (OR=1.05, 95% CI=0.93 to 1.17, P=0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife using our lifecourse approach (OR=1.37, 95% CI=1.28 to 1.46, P=7x10-12). InterpretationThese findings suggest that adiposity in childhood and adulthood are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse. This inference would not be possible without the application of human genetic data, emphasizing the value of this approach in uncovering risk factors that begin to exert their influence on disease at early stages in life. FundingThe Medical Research Council and the British Heart Foundation.