Cumulative genetic risk for asthma contributes to disease severity in children with asthma.

BACKGROUND

Childhood-onset asthma is highly heritable, with nearly 200 risk loci identified in genome-wide association studies. Aggregated polygenic risk scores (PRSs) can be used to quantify genetic predisposition to asthma, but their power to predict asthma severity in multiancestral groups has not been previously evaluated.

OBJECTIVE

Our aim was to examine the predictive power of biobank-derived asthma PRSs in 4 multiancestry asthma study cohorts of children living in US urban environments.

METHODS

We generated PRSs for asthma, derived from a large-scale genome-wide association meta-analysis, and assessed genetic predictions across different subphenotypes of asthma and tested for associations between genetic asthma risk and measures of asthma severity.

RESULTS

PRS prediction was significantly stronger for more symptomatic asthma phenotypes (P < .001), and scores were significantly higher in difficult-to-control versus easy-to-control asthma (P = .02). Genetic risk was also significantly associated with more frequent exacerbations (P = .03), higher blood eosinophil levels (P = .01), and lower lung function (P < .001).

CONCLUSION

Cumulative genetic risk for asthma is associated with disease severity and exacerbation risk in children with asthma.