Abstract
BACKGROUNDSleep is increasingly recognized as essential to human health, yet the adverse health consequences of acute sleep deprivation are unknown. We hypothesized that acute sleep deprivation is associated with health outcomes and modulated by sleep-associated genotypes.METHODSLocally estimated scatterplot smoothing (LOESS) was performed on sleep estimates from Fitbit users (n = 14,681) between June 1, 2016, and July 1, 2022. Dates when population minutes slept were less than the 90% confidence interval of the LOESS regression were named acute sleep deprivation events (ASDEs). Phenome-wide disease incidence among the All of Us Research Program population (n = 287,012) in the 10 days after ASDE was compared with a preceding reference period by McNemar's test. Circadian rhythm-associated and sleep duration-associated SNPs were screened to identify genotypes associated with shorter ASDE sleep duration. Influences of sleep and circadian genotype on post-ASDE influenza risk were modeled using binomial family generalized estimating equations.RESULTSWe identified 32 ASDEs spanning major national events. A phenome-wide screen found increased risk of influenza (odds ratio = 1.54 [1.40, 1.70], P = 1.00 × 10-18) following ASDEs. Fifty-six SNPs were associated with decreased sleep duration on ASDEs. Higher quantiles of ASDE-related SNP genotype burden were associated with less ASDE sleep duration and a greater risk of influenza-associated health care visits.CONCLUSIONMajor national events are associated with acute sleep deprivation and greater influenza risk, which is amplified by sleep genotypes. These findings should inform public health vigilance surrounding major national events.FUNDINGWoodNext Foundation; NIH grants T32HL129964, K08ES037420, R01HL124021, R01HL122596, and R01HL151228; American Heart Association grants 24SFRNCCN1276089 and 24SFRNPCN1280228; and the United Therapeutics Jenesis Innovative Research Awards, the Pulmonary Hypertension Association, the McKamish Family Foundation, the Hemophilia Center of Western Pennsylvania, and the Institute for Transfusion Medicine.