Dataset Information

Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study.

ABSTRACT:

Background

Vitamin D deficiency and insufficiency have been established to be strongly associated with increased overall mortality and deaths from specific aging-related diseases. Recently, an epigenetic "mortality risk score" (MS) based on whole blood DNA methylation at the 10 most prominent mortality-related cytosine-phosphate-guanine (CpG) sites has also been found to be highly related to all-cause mortality. This study aimed to explore whether vitamin D status, defined by serum 25-hydroxyvitamin D [25(OH)D] concentrations, is associated with the MS and to what extent both indicators are individually and jointly capable of predicting all-cause mortality in a general population sample of older adults.

Results

The MS was derived from the blood DNA methylation profiles measured by Illumina Human Methylation 450K Beadchip, and serum 25(OH)D concentration was measured among 1467 participants aged 50-75 of the German ESTHER cohort study. There was no association between vitamin D status and the MS at baseline, but both metrics were prominently and independently associated with all-cause mortality during a median follow-up of 15.2 years. The combination of both indicators showed the potential to be a particularly strong prognostic index for all-cause mortality. Participants with vitamin D deficiency (?5 CpG sites with aberrant methylation) had almost sixfold mortality (hazard ratio 5.79, 95% CI 3.06-10.94) compared with participants with sufficient vitamin D (??50 nmol/L) and a low MS (0-1 CpG site with aberrant methylation).

Conclusions

This study suggests that vitamin D and the MS are strong independent predictors of all-cause mortality in older adults.

SUBMITTER: Gao X

PROVIDER: S-EPMC6011585 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study.

Gao Xu X Zhang Yan Y Schöttker Ben B Brenner Hermann H

Clinical epigenetics 20180620

<h4>Background</h4>Vitamin D deficiency and insufficiency have been established to be strongly associated with increased overall mortality and deaths from specific aging-related diseases. Recently, an epigenetic "mortality risk score" (MS) based on whole blood DNA methylation at the 10 most prominent mortality-related cytosine-phosphate-guanine (CpG) sites has also been found to be highly related to all-cause mortality. This study aimed to explore whether vitamin D status, defined by serum 25-hy ...[more]

PMID: 29977410

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Project description:BackgroundVitamin K-dependent proteins in vascular tissue affect vascular stiffness and calcification, which is associated with cardiovascular disease (CVD) and all-cause mortality.ObjectiveTo determine the association of circulating vitamin K concentrations with CVD and all-cause mortality by conducting a participant-level meta-analysis.MethodsWe obtained individual participant-level data from the Health, Aging, and Body Composition Study, the Multi-Ethnic Study of Atherosclerosis, and the Framingham Offspring Study, known cohorts with available measures of fasting circulating phylloquinone (vitamin K-1) and confirmed CVD events and mortality. Circulating phylloquinone was measured in a central laboratory from fasting blood samples and categorized as ≤0.5 nmol/L, >0.5-1.0 nmol/L, and >1.0 nmol/L. Multivariable Cox proportional hazard regression with multiple imputations was used to evaluate the association of circulating phylloquinone with incident CVD and all-cause mortality risk.ResultsAmong 3891 participants (mean age 65 ± 11 y; 55% women; 35% nonwhite), there were 858 incident CVD events and 1209 deaths over a median of 13.0 y. The risk of CVD did not significantly differ according to circulating phylloquinone [fully adjusted HR (95% CI) relative to >1.0 nmol/L: ≤0.5 nmol/L, 1.12 (0.94, 1.33); >0.5-1.0 nmol/L, 1.02 (0.86, 1.20)]. Participants with ≤0.5 nmol/L circulating phylloquinone had an adjusted 19% higher risk of all-cause mortality compared with those with >1.0 nmol/L [fully adjusted HR (95% CI): 1.19 (1.03, 1.38)]. Mortality risk was similar in participants with >0.5-1.0 nmol/L compared with >1.0 nmol/L [fully adjusted HR (95% CI): 1.04 (0.92, 1.17)].ConclusionsLow circulating phylloquinone concentrations were associated with an increased risk of all-cause mortality, but not of CVD. Additional studies are needed to clarify the mechanism underlying this association and evaluate the impact of increased phylloquinone intake on cardiovascular and other health outcomes in individuals with low vitamin K status.

Dataset Information

Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study.

Background

Results

Conclusions

Publications

Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study.

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