Light at night and modeled circadian disruption predict higher risk of mortality: A prospective study in >88,000 participants

Importance Light at night disrupts human circadian rhythms, which are critical for maintaining optimal health. Circadian disruption accompanies poor health outcomes that precede premature mortality, including cardiometabolic diseases. However, links between personal night light exposure and premature mortality risk have not been established. Objective To characterize the association of light at night with all-cause and cardiometabolic mortality risks and to understand the role of circadian disruption in these associations by applying a computational model of the response of the human circadian pacemaker to light. Design Prospective cohort study. Setting United Kingdom. Participants UK Biobank cohort, N=88,904, aged 62.4±7.8 years, 57% female. Exposure Participants wore activity tracking watches with light sensors for one week between 2013-2016. Twenty-four-hour light exposure profiles were extracted for each participant, and day-time and night-time hours were defined by factor analysis. A validated mathematical model of the human circadian pacemaker was applied to model circadian amplitude and phase from weekly light data. Main Outcome Cause-specific mortality (National Health Service) recorded in 2,605 participants across a mean (±SD) follow-up period of 6.31±0.83 years after light/activity tracking. Results Risk of all-cause mortality was higher in participants in the 90th-100th percentiles of night-light exposure (HR[95%CI]=1.30[1.15-1.48]), and for those between the 70th-90th percentiles (HR=1.16[1.04-1.28]), compared to the darkest 50%. Participants in the 90th-100th percentiles of night-light exposure also had higher risk of cardiometabolic mortality (HR=1.41[1.07-1.85]). Higher circadian amplitude predicted lower risks of all-cause mortality (HR = 0.94[0.91-0.97] per SD) and cardiometabolic mortality (HR=0.90[0.83-0.96]), and circadian phase that deviated from the group average predicted higher risks of all-cause mortality (HR=1.33[1.17-1.51]) and cardiometabolic mortality (HR=1.48[1.12-1.97]). These findings were robust to adjustment for age, sex, ethnicity, and sociodemographic and lifestyle factors. Conclusions and Relevance Minimizing exposure to light at night and keeping regular light-dark patterns that enhance circadian rhythms may promote cardiometabolic health and longevity. Question Is light exposure at night associated with risk of premature mortality? Findings Exposure to brighter light at night, recorded with personal light sensors in >88,000 participants, was associated with higher risk of mortality across a subsequent 6-year period. Computational modeling indicated that disrupted circadian rhythms may explain this higher mortality risk. Meaning Avoiding light at night may be a cost-effective and accessible recommendation for promoting health and longevity. ### Competing Interest Statement AJKP and SWC received research funding from Versalux and Delos, and are co-founders and co-directors of Circadian Health Innovations PTY LTD. SWC has also consulted for Dyson, and received research funding from Beacon Lighting. PO co-founded Axivity Ltd, and was a Director until 2015. DPW: none; ACB: none; RS: none; JML: none; MKR: none. ### Funding Statement This work was supported by the NIHR Manchester Biomedical Research Centre. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank has ethical approval from the North West Multi-centre Research Ethics Committee (https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/about-us/ethics). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data underlying this work are available at the UK Biobank website, upon application: . Scripts for data handling and analysis will be made available upon request by Daniel P. Windred [daniel.windred{at}monash.edu].