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 promine...

Full description

Bibliographic Details
Main Authors: Xu Gao, Yan Zhang, Ben Schöttker, Hermann Brenner
Format: Article
Language:English
Published: BMC 2018-06-01
Series:Clinical Epigenetics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13148-018-0515-y
_version_ 1811324686244511744
author Xu Gao
Yan Zhang
Ben Schöttker
Hermann Brenner
author_facet Xu Gao
Yan Zhang
Ben Schöttker
Hermann Brenner
author_sort Xu Gao
collection DOAJ
description 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 (< 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). Conclusions This study suggests that vitamin D and the MS are strong independent predictors of all-cause mortality in older adults.
first_indexed 2024-04-13T14:19:55Z
format Article
id doaj.art-87c67bb3dc364c309807fc91fdffb2b8
institution Directory Open Access Journal
issn 1868-7075
1868-7083
language English
last_indexed 2024-04-13T14:19:55Z
publishDate 2018-06-01
publisher BMC
record_format Article
series Clinical Epigenetics
spelling doaj.art-87c67bb3dc364c309807fc91fdffb2b82022-12-22T02:43:32ZengBMCClinical Epigenetics1868-70751868-70832018-06-0110111010.1186/s13148-018-0515-yVitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort studyXu Gao0Yan Zhang1Ben Schöttker2Hermann Brenner3Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)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 (< 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). Conclusions This study suggests that vitamin D and the MS are strong independent predictors of all-cause mortality in older adults.http://link.springer.com/article/10.1186/s13148-018-0515-yDNA methylationEpigenetic mortality risk scoreVitamin DAll-cause mortalityEpigenetic epidemiologyPrecision medicine
spellingShingle Xu Gao
Yan Zhang
Ben Schöttker
Hermann Brenner
Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study
Clinical Epigenetics
DNA methylation
Epigenetic mortality risk score
Vitamin D
All-cause mortality
Epigenetic epidemiology
Precision medicine
title Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study
title_full Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study
title_fullStr Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study
title_full_unstemmed Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study
title_short Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study
title_sort vitamin d status and epigenetic based mortality risk score strong independent and joint prediction of all cause mortality in a population based cohort study
topic DNA methylation
Epigenetic mortality risk score
Vitamin D
All-cause mortality
Epigenetic epidemiology
Precision medicine
url http://link.springer.com/article/10.1186/s13148-018-0515-y
work_keys_str_mv AT xugao vitamindstatusandepigeneticbasedmortalityriskscorestrongindependentandjointpredictionofallcausemortalityinapopulationbasedcohortstudy
AT yanzhang vitamindstatusandepigeneticbasedmortalityriskscorestrongindependentandjointpredictionofallcausemortalityinapopulationbasedcohortstudy
AT benschottker vitamindstatusandepigeneticbasedmortalityriskscorestrongindependentandjointpredictionofallcausemortalityinapopulationbasedcohortstudy
AT hermannbrenner vitamindstatusandepigeneticbasedmortalityriskscorestrongindependentandjointpredictionofallcausemortalityinapopulationbasedcohortstudy