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

Background Separating 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. Methods 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. Findings We 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=7×10−12). Interpretation These 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. Funding The Medical Research Council and the British Heart Foundation. ### Competing Interest Statement TGR is a full-time employee of GlaxoSmithKline outside of this work. ### Funding Statement This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC\_UU\_00011/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: N/A I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data used in this study is based of previously published summary-level datasets.