Approved research

Estimate the causal effect of asthma on risk of obesity using Mendelian randomization

Lay summary

This project aims to estimate the causal effect of asthma on obesity via Mendelian randomization, which uses the genetic variants as instrumental variables (IVs). We plan to construct a polygenic risk score of asthma-related genetic variants from the GWAS Catalog, examine the IV assumptions and validate polygenic risk score as a non-weak instrument, and then perform the two-stage method to estimate the causal effect of asthma on obesity accounting for measured confounding factor. Epidemiological studies have demonstrated an association between asthma and obesity, two major public health concerns across the globe. Obesity is the one of most common asthma co-morbidities. In the Southern California Children's Health Study, children with a diagnosis of asthma at cohort enrollment were found at higher risk of developing obesity during childhood and adolescence than those who were asthma-free; while the use of asthma rescue medications reduced the risk of becoming obese. Conflicting results on whether obesity is causal for asthma using Mendelian randomization have been reported, yet whether asthma is causal for obesity has not been investigated using the Mendelian randomization approach. We hope to boost the power and precision in estimating the causal effect, if any, of the risk factor asthma on obesity with the help of big sample size that UK Biobank provides. In recent decades, the prevalence of both asthma and obesity has been increasing worldwide, posing a great challenge to public health. By elucidating the causal link between asthma and obesity, we hope to gain insights about causal pathway from asthma-related genetic variants to obesity and to suggest that public health interventions designed to reduce asthma may also help to limit the rising risk of obesity. We are requesting the whole cohort.