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

BackgroundVitamin 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.ResultsThe 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 (< 30 nmol/L) and high MS (> 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).ConclusionsThis study suggests that vitamin D and the MS are strong independent predictors of all-cause mortality in older adults.