Impact of lifestyle factors on adult-onset asthma in genetically high-risk individuals

Background: Asthma is a heterogeneous disease influenced by genetic and environmental factors. Identifying high-risk individuals for developing asthma is a major goal of primary prevention. Recent studies have reported that genetic factors can predict high-risk groups for various diseases. However, the understanding of genetically high-risk individuals for adult-onset asthma, which could be potential targets for preventive interventions, remains limited. Using a polygenic risk score (PRS), we identified a group of individuals at a genetically high risk for adult-onset asthma and examined their characteristics, as well as the degree of risk reduction through lifestyle factors. Methods: Using the asthma PRS provided by the UK Biobank, we identified a genetically high-risk group among unrelated White British individuals, including those with adult-onset asthma and a control group. We analysed the association between asthma-related lifestyle factors and adult-onset asthma in the high-risk group. Additionally, we conducted Kaplan-Meier analysis to investigate the cumulative incidence of adult-onset asthma by age of onset according to genetic risk and lifestyle status. Results: The high-risk group for adult-onset asthma had a 2.26 times higher risk of developing asthma compared to the average-risk group. Within the high-risk group, lifestyle factors, such as obesity-related traits, stress, insomnia, and snoring, were significantly associated with adult-onset asthma. Among individuals in the high-risk group, adhering to a favourable lifestyle can reduce the lifetime risk of adult-onset asthma by up to 40% compared to those with an unfavourable lifestyle. Conclusions: Based on this study, we suggest that the PRS can identify individuals at high risk of developing adult-onset asthma. Furthermore, our findings indicate that individuals with a genetically high risk may reduce their disease risk through appropriate lifestyle modifications, emphasising their potential to benefit significantly from primary prevention strategies. However, as this study is cross-sectional and assumes that lifestyle factors have remained unchanged, further prospective studies are required to validate these findings.