Highlighting the importance of healthy sleep patterns in the risk of adult asthma under the combined effects of genetic susceptibility: a large-scale prospective cohort study of 455 405 participants

Bowen Xiang, Mengxiao Hu, Haiyang Yu, Yike Zhang, Qing Wang, Fuzhong Xue

Individuals with asthma usually have comorbid sleep disturbances; however, whether sleep quality affects asthma risk is still unclear. We aimed to determine whether poor sleep patterns could increase the risk of asthma and whether healthy sleep patterns could mitigate the adverse effect of genetic susceptibility. A large-scale prospective study was performed in the UK Biobank cohort involving 455 405 participants aged 38-73 years. Polygenic risk scores (PRSs) and comprehensive sleep scores, including five sleep traits, were constructed. A multivariable Cox proportional hazards regression model was used to investigate the independent and combined effects of sleep pattern and genetic susceptibility (PRS) on asthma incidence. Subgroup analysis across sex and sensitivity analysis, including a 5-year lag, different covariate adjustments and repeat measurements were performed. A total of 17 836 individuals were diagnosed with asthma during over 10 years of follow-up. Compared with the low-risk group, the HRs and 95% CIs for the highest PRS group and the poor sleep pattern group were 1.47 (95% CI: 1.41 to 1.52) and 1.55 (95% CI: 1.45 to 1.65), respectively. A combination of poor sleep and high genetic susceptibility led to a twofold higher risk compared with the low-risk combination (HR (95% CI): 2.22 (1.97 to 2.49), p<0.001). Further analysis showed that a healthy sleep pattern was associated with a lower risk of asthma in the low, intermediate and high genetic susceptibility groups (HR (95% CI): 0.56 (0.50 to 0.64), 0.59 (0.53 to 0.67) and 0.63 (0.57 to 0.70), respectively). Population-attributable risk analysis indicated that 19% of asthma cases could be prevented when these sleep traits were improved. Individuals with poor sleep patterns and higher genetic susceptibility have an additive higher asthma risk. A healthy sleep pattern reflected a lower risk of asthma in adult populations and could be beneficial to asthma prevention regardless of genetic conditions. Early detection and management of sleep disorders could be beneficial to reduce asthma incidence.