Dataset Information

Association between sleep disordered breathing and epigenetic age acceleration: Evidence from the Multi-Ethnic Study of Atherosclerosis.

ABSTRACT:

Background

Sleep disordered breathing (SDB) is a common disorder that results in oxidative stress and inflammation and is associated with multiple age-related health outcomes. Epigenetic age acceleration is a DNA methylation (DNAm)-based marker of fast biological aging. We examined the associations of SDB traits with epigenetic age acceleration.

Methods

A sample of 622 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) had blood DNAm measured and underwent Type 2 in-home polysomnography that assessed apnea-hypopnea index (AHI), percentage of sleep time with oxygen saturation lower than 90% (Per90), and arousal index. DNAm data provided measures of DNAm-Age acceleration and DNAm-PhenoAge acceleration. The association of each SDB trait with age acceleration was estimated using linear regression, controlling for covariates. In secondary analyses, we studied the associations of SDB traits with epigenetic age acceleration 2-10 years after sleep study in 530 individuals from the Framingham Heart Study (FHS).

Findings

In MESA, AHI was associated with greater DNAm-PhenoAge acceleration (? = 0.03; 95% CI [0.001, 0.06]). Arousal index was associated with greater DNAm-Age acceleration (? = 0.04; 95% CI [0.01, 0.07]). Both associations were stronger in women than men. In the secondary FHS analyses, Per90 was associated with greater DNAm-Age acceleration and this association was stronger in men.

Interpretation

More severe SDB was associated with epigenetic age acceleration in both cohorts. Future work should prospectively study short- and long-term effects of SDB, and whether treatment reduces epigenetic age acceleration among those individuals with SBD.

Funding

National Institutes of Health.

SUBMITTER: Li X

PROVIDER: S-EPMC6921369 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Association between sleep disordered breathing and epigenetic age acceleration: Evidence from the Multi-Ethnic Study of Atherosclerosis.

Li Xiaoyu X Joehanes Roby R Hoeschele Ina I Rich Stephen S SS Rotter Jerome I JI Levy Daniel D Liu Yongmei Y Redline Susan S Sofer Tamar T

EBioMedicine 20191121

<h4>Background</h4>Sleep disordered breathing (SDB) is a common disorder that results in oxidative stress and inflammation and is associated with multiple age-related health outcomes. Epigenetic age acceleration is a DNA methylation (DNAm)-based marker of fast biological aging. We examined the associations of SDB traits with epigenetic age acceleration.<h4>Methods</h4>A sample of 622 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) had blood DNAm measured and underwent Type 2 i ...[more]

PMID: 31761615

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Project description:RationaleThere are conflicting findings regarding the link between sleep apnea and cognitive dysfunction.ObjectivesInvestigate associations between indicators of sleep-disordered breathing (SDB) and cognitive function in the Multi-Ethnic Study of Atherosclerosis and assess effect modification by the apolipoprotein ε-4 (APOE-ε4) allele.MethodsA diverse population (N = 1,752) underwent type 2 in-home polysomnography, which included measurement of percentage sleep time less than 90% oxyhemoglobin saturation (%Sat < 90%) and apnea-hypopnea index (AHI). Epworth Sleepiness Scale score (ESS) and sleep apnea syndrome (SAS; AHI ≥ 5 and ESS > 10) were also analyzed. Cognitive outcomes included the Cognitive Abilities Screening Instrument; Digit Symbol Coding (DSC) test; and Digit Span Tests (DST) Forward and Backward.ResultsParticipants were 45.4% men, aged 68.1 years (SD, 9.1 yr) with a median AHI of 9.0 and mean ESS of 6.0. Approximately 9.7% had SAS, and 26.8% had at least one copy of the APOE-ε4 allele. In adjusted analyses, a 1-SD increase in %Sat < 90% and ESS score were associated with a poorer attention and memory assessed by the DST Forward score (β = -0.12 [SE, 0.06] and β = -0.13 [SE, 0.06], respectively; P ≤ 0.05). SAS and higher ESS scores were also associated with poorer attention and processing speed as measured by the DSC (β = -0.69 [SE, 0.35] and β = -1.42 [SE, 0.35], respectively; P < 0.05). The presence of APOE-ε4 allele modified the associations of %Sat < 90% with DST forward and of ESS with DSC (Pinteraction ≤ 0.05).ConclusionsOvernight hypoxemia and sleepiness were associated with cognition. The average effect estimates were small, similar to effect estimates for several other individual dementia risk factors. Associations were strongest in APOE-ε4 risk allele carriers. Our results (1) suggest that SDB be considered among a group of modifiable dementia risk factors, and (2) highlight the potential vulnerability of APOE-ε4 risk allele carriers with SDB.

Project description:ObjectiveTo examine the association between sleep-disordered breathing and stroke outcomes, and determine the contribution of sleep-disordered breathing to outcome disparities in Mexican Americans.MethodsIschemic stroke patients (n = 995), identified from the population-based Brain Attack Surveillance in Corpus Christi Project (2010-2015), were offered participation in a sleep-disordered breathing study including a home sleep apnea test (ApneaLink Plus). Sleep-disordered breathing (respiratory event index ≥10) was determined soon after stroke. Neurologic, functional, cognitive, and quality of life outcomes were assessed at 90 days poststroke. Regression models were used to assess associations between sleep-disordered breathing and outcomes, adjusted for sociodemographics, prestroke function and cognition, health-risk behaviors, stroke severity, and vascular risk factors.ResultsMedian age was 67 years (interquartile range [IQR] = 59-78); 62.1% were Mexican American. Median respiratory event index was 14 (IQR = 6-25); 62.8% had sleep-disordered breathing. Sleep-disordered breathing was associated with worse functional outcome (mean difference in activities of daily living/instrumental activities of daily living score = 0.15, 95% confidence interval [CI] = 0.01-0.28) and cognitive outcome (mean difference in modified Mini-Mental State Examination = -2.66, 95% CI = -4.85 to -0.47) but not neurologic or quality of life outcomes. Sleep-disordered breathing accounted for 9 to 10% of ethnic differences in functional and cognitive outcome and was associated with cognitive outcome more strongly for Mexican Americans (β = -3.97, 95% CI = -6.63 to -1.31) than non-Hispanic whites (β = -0.40, 95% CI = -4.18 to 3.39, p-interaction = 0.15).InterpretationSleep-disordered breathing is associated with worse functional and cognitive function at 90 days poststroke. These outcomes are reasonable endpoints for future trials of sleep-disordered breathing treatment in stroke. If effective, sleep-disordered breathing treatment may somewhat lessen ethnic stroke outcome disparities. ANN NEUROL 2019;86:241-250.

Dataset Information

Association between sleep disordered breathing and epigenetic age acceleration: Evidence from the Multi-Ethnic Study of Atherosclerosis.

Background

Methods

Findings

Interpretation

Funding

Publications

Association between sleep disordered breathing and epigenetic age acceleration: Evidence from the Multi-Ethnic Study of Atherosclerosis.

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