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Health outcomes after national acute sleep deprivation events among the American public
Neil J. Kelly, Rahul Chaudhary, Wadih El Khoury, Nishita Kalepalli, Jesse Wang, Priya Patel, Irene N. Chan, Haris Rahman, Aisha Saiyed, Anisha N. Shah, Colleen A. McClung, Satoshi Okawa, Seyed Mehdi Nouraie, Stephen Y. Chan
Neil J. Kelly, Rahul Chaudhary, Wadih El Khoury, Nishita Kalepalli, Jesse Wang, Priya Patel, Irene N. Chan, Haris Rahman, Aisha Saiyed, Anisha N. Shah, Colleen A. McClung, Satoshi Okawa, Seyed Mehdi Nouraie, Stephen Y. Chan
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Clinical Research and Public Health Genetics Public Health

Health outcomes after national acute sleep deprivation events among the American public

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Abstract

BACKGROUND Sleep 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.METHODS Locally 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.RESULTS We 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.CONCLUSION Major 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.FUNDING WoodNext 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.

Authors

Neil J. Kelly, Rahul Chaudhary, Wadih El Khoury, Nishita Kalepalli, Jesse Wang, Priya Patel, Irene N. Chan, Haris Rahman, Aisha Saiyed, Anisha N. Shah, Colleen A. McClung, Satoshi Okawa, Seyed Mehdi Nouraie, Stephen Y. Chan

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Figure 4

Circadian and sleep genotypes are associated with sleep duration and post-ASDE influenza risk.

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Circadian and sleep genotypes are associated with sleep duration and pos...
(A) Volcano plot of SNP allele combinations associated with shorter sleep duration on ASDEs. SNPs associated with significantly shorter sleep duration than the AoU population on ASDEs after correction for false discovery rate are highlighted. (B and C) Genotyped AoU participants were grouped into quantiles based on their number of short sleep–associated SNP allele combinations. Sleep duration in the genotyped AoU Fitbit population was decreased by short sleep genotype quantiles on ASDEs (B) and overall (C). (D) Forest plot of log10(odds ratio) of influenza diagnosis as a function of post-ASDE timing overall and grouped by short sleep genotype quantile with adjustment for age at ASDE, sex chromosome ploidy, time-weighted average weekly positive influenza tests, and genomic ancestry in a generalized estimating equation model. Comparisons in ASDE sleep duration between SNP genotypes as well as between ASDE sleep duration quantiles were performed using Mann-Whitney test. Dashed line on violin plot shows median; dotted lines show interquartile range. P < 0.05 was considered statistically significant. Pintxn, interaction P value (short sleep genotype quantile × post-ASDE timing).

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