Sleep Regularity and Mortality: A Prospective Analysis in the UK Biobank

Reviewer #1 (Public Review):

This manuscript provides important evidence on the association between sleep regularity and mortality in the UK Biobank, which is a popular topic in recent sleep and circadian research in population-based studies. The analysis reported robust associations between sleep irregularity and increased total, CVD and cancer mortality, and provided evidence to support the role of sleep and circadian health in disease progression and longevity in human populations. The Sleep Regularity Index (SRI) used in this study is a novel metric that quantifies the consistency in rest-activity rhythms over consecutive 24 hour periods, thus providing objective assessment of potential circadian disruption. The study is based on a large accelerometer study with validated follow-up of incident diseases and deaths. The data quality and large sample size strengthen the credibility of the conclusion. Overall, the analyses are appropriately done and the manuscript is clearly written. Additional justification for the assessment of nonlinearity and further subgroup analyses would further improve the manuscript.

Reviewer #2 (Public Review):

This interesting research commendably revealed the association between sleep regularity and mortality. However, as authors acknowledged, the analysis can not accurately identify the cause and effect. In my opinion, the causality is important for this topic, cuz, sleep regularity and health (e.g. chronic disease) were long-term simultaneous status, especially given the participants are older. I suggest that the author could utilize MR analysis to find out for more evidence.