Dataset Information

Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality.

ABSTRACT: With epigenome-wide mapping of DNA methylation, a number of novel smoking-associated loci have been identified.We aimed to assess dose-response relationships of methylation at the top hits from the epigenome-wide methylation studies with smoking exposure as well as with total and cause-specific mortality.In a population-based prospective cohort study in Germany, methylation was quantified in baseline blood DNA of 1,000 older adults by the Illumina 450K assay. Deaths were recorded during a median follow-up of 10.3 years. Dose-response relationships of smoking exposure with methylation at nine CpGs were modeled by restricted cubic spline regression. Associations of individual and aggregate methylation patterns with all-cause, cardiovascular, and cancer mortality were assessed by multiple Cox regression.Clear dose-response relationships with respect to current and lifetime smoking intensity were consistently observed for methylation at six of the nine CpGs. Seven of the nine CpGs were also associated with mortality outcomes to various extents. A methylation score based on the top two CpGs (cg05575921 and cg06126421) showed the strongest associations with all-cause, cardiovascular, and cancer mortality, with adjusted hazard ratios (95% CI) of 3.59 (2.10, 6.16), 7.41 (2.81, 19.54), and 2.48 (1.01, 6.08), respectively, for participants with methylation levels in the lowest quartile at both CpGs. Adding methylation at those two CpGs into a model that included the variables of the Systematic Coronary Risk Evaluation chart for fatal cardiovascular risk prediction improved the predictive discrimination.The novel methylation biomarkers are highly informative for both smoking exposure and smoking-related mortality outcomes. In particular, these biomarkers may substantially improve cardiovascular risk prediction. Nevertheless, the findings of the present study need to be further validated in additional large longitudinal studies.Zhang Y, Schöttker B, Florath I, Stock C, Butterbach K, Holleczek B, Mons U, Brenner H. 2016. Smoking-associated DNA methylation biomarkers and their predictive value for all-cause and cardiovascular mortality. Environ Health Perspect 124:67-74; http://dx.doi.org/10.1289/ehp.1409020.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4710597 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality.

Zhang Yan Y Schöttker Ben B Florath Ines I Stock Christian C Butterbach Katja K Holleczek Bernd B Mons Ute U Brenner Hermann H

Environmental health perspectives 20150527 1

<h4>Background</h4>With epigenome-wide mapping of DNA methylation, a number of novel smoking-associated loci have been identified.<h4>Objectives</h4>We aimed to assess dose-response relationships of methylation at the top hits from the epigenome-wide methylation studies with smoking exposure as well as with total and cause-specific mortality.<h4>Methods</h4>In a population-based prospective cohort study in Germany, methylation was quantified in baseline blood DNA of 1,000 older adults by the Ill ...[more]

PMID: 26017925

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Project description:AimsThe aim of the present study is to determine the pooled predictive value of carotid distensibility coefficient (DC) for cardiovascular (CV) diseases and all-cause mortality.BackgroundArterial stiffness is associated with future CV events. Aortic pulse wave velocity is a commonly used predictor for CV diseases and all-cause mortality; however, its assessment requires specific devices and is not always applicable in all patients. In addition to the aortic artery, the carotid artery is also susceptible to atherosclerosis, and is highly accessible because of the surficial property. Thus, carotid DC, which indicates the intrinsic local stiffness of the carotid artery and may be determined using ultrasound and magnetic resonance imaging, is of interest for the prediction. However, the role of carotid DC in the prediction of CV diseases and all-cause mortality has not been thoroughly characterized, and the pooled predictive value of carotid DC remains unclear.MethodsA meta-analysis, which included 11 longitudinal studies with 20361 subjects, was performed.ResultsCarotid DC significantly predicted future total CV events, CV mortality and all-cause mortality. The pooled risk ratios (RRs) of CV events, CV mortality and all-cause mortality were 1.19 (1.06-1.35, 95%CI, 9 studies with 18993 subjects), 1.09 (1.01-1.18, 95%CI, 2 studies with 2550 subjects) and 1.65 (1.15-2.37, 95%CI, 6 studies with 3619 subjects), respectively, for the subjects who had the lowest quartile of DC compared with their counterparts who had higher quartiles. For CV events, CV mortality and all-cause mortality, a decrease in DC of 1 SD increased the risk by 13%, 6% and 41% respectively, whereas a decrease in DC of 1 unit increased the risk by 3%, 1% and 6% respectively.ConclusionsCarotid DC is a significant predictor of future CV diseases and all-cause mortality, which may facilitate the identification of high-risk patients for the early diagnosis and prompt treatment of CV diseases.

Project description:BackgroundDNA methylation patterns associated with habitual diet have not been well studied.MethodsDiet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality.ResultsWe identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10-6).ConclusionsHabitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

Dataset Information

Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality.

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Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality.

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