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DNA methylation age of blood predicts all-cause mortality in later life.

ABSTRACT: BACKGROUND:DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. RESULTS:Here we test whether differences between people's chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (?age) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between ?age and mortality. A 5-year higher ?age is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher ?age. A pedigree-based heritability analysis of ?age was conducted in a separate cohort. The heritability of ?age was 0.43. CONCLUSIONS:DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.

SUBMITTER: Marioni RE

PROVIDER: S-EPMC4350614 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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DNA methylation age of blood predicts all-cause mortality in later life.

Marioni Riccardo E RE Shah Sonia S McRae Allan F AF Chen Brian H BH Colicino Elena E Harris Sarah E SE Gibson Jude J Henders Anjali K AK Redmond Paul P Cox Simon R SR Pattie Alison A Corley Janie J Murphy Lee L Martin Nicholas G NG Montgomery Grant W GW Feinberg Andrew P AP Fallin M Daniele MD Multhaup Michael L ML Jaffe Andrew E AE Joehanes Roby R Schwartz Joel J Just Allan C AC Lunetta Kathryn L KL Murabito Joanne M JM Starr John M JM Horvath Steve S Baccarelli Andrea A AA Levy Daniel D Visscher Peter M PM Wray Naomi R NR Deary Ian J IJ

Genome biology 20150130

<h4>Background</h4>DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age.<h4>Results</h4>Here we test whether differences between people's chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in fou ...[more]

PMID: 25633388

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Project description:BACKGROUND:DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer. METHODS:We retrieved information of 1076 breast cancer patients from Genomic Data Commons (GDC) data portal on March 30, 2017, including breast cancer DNAm profiling, demographic features, clinicopathological parameters, recurrence, and all-cause fatality. Horvath's method was applied to calculate the DNAm age. Cox proportional hazards regression models were used to test the associations between DNAm age of the cancerous tissues and the prognosis (recurrence of breast cancer and all-cause fatality) with or without adjusting for chronological age and clinicopathological parameters. RESULTS:The DNAm age was markedly decelerated in the patients who were premenopausal, ER or PR negative, HER2-enriched or basal-like than their counterparts. In the first five-year follow-up dataset for survival, every ten-year increase in DNAm age was associated with a 15% decrease in fatality; subjects with DNAm age in the second (HR: 0.52; 95%CI: 0.29-0.92), the third (HR: 0.49; 95%CI: 0.27-0.87) and the fourth quartile (HR: 0.38; 95%CI: 0.20-0.72) had significant longer survival time than those in the first quartile. In the first five-year follow-up dataset for recurrence, every ten-year increase in DNAm age was associated with a 14% decrease of the recurrence; in the categorical analysis, a clear dose-response was shown (P for trend =0.02) and the fourth quartile was associated with a longer recurrence free survival (HR: 0.32; 95%CI: 0.14-0.74). In the full follow-up dataset, similar results were obtained. CONCLUSIONS:DNAm age of breast cancer tissue, which associated with menopausal status and pathological features, was a strong independent predictor of the prognosis. It was suggested that the prognosis of breast cancer was related to intrinsic biological changes and specific molecular targets for treatment of breast cancer may be implicit.

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.

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DNA methylation age of blood predicts all-cause mortality in later life.

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DNA methylation age of blood predicts all-cause mortality in later life.

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