Dataset Information

Education and Lifestyle Factors Are Associated with DNA Methylation Clocks in Older African Americans.

ABSTRACT: DNA methylation (DNAm) clocks are important biomarkers of cellular aging and are associated with a variety of age-related chronic diseases and all-cause mortality. Examining the relationship between education and lifestyle risk factors for age-related diseases and multiple DNAm clocks can increase the understanding of how risk factors contribute to aging at the cellular level. This study explored the association between education or lifestyle risk factors for age-related diseases and the acceleration of four DNAm clocks, including intrinsic (IEAA) and extrinsic epigenetic age acceleration (EEAA), PhenoAge acceleration (PhenoAA), and GrimAge acceleration (GrimAA) in the African American participants of the Genetic Epidemiology Network of Arteriopathy. We performed both cross-sectional and longitudinal analyses. In cross-sectional analyses, gender, education, BMI, smoking, and alcohol consumption were all independently associated with GrimAA, whereas only some of them were associated with other clocks. The effect of smoking and education on GrimAA varied by gender. Longitudinal analyses suggest that age and BMI continued to increase GrimAA, and that age and current smoking continued to increase PhenoAA after controlling DNAm clocks at baseline. In conclusion, education and common lifestyle risk factors were associated with multiple DNAm clocks. However, the association with each risk factor varied by clock, which suggests that different clocks may capture adverse effects from different environmental stimuli.

SUBMITTER: Zhao W

PROVIDER: S-EPMC6747433 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Education and Lifestyle Factors Are Associated with DNA Methylation Clocks in Older African Americans.

Zhao Wei W Ammous Farah F Ratliff Scott S Liu Jiaxuan J Yu Miao M Mosley Thomas H TH Kardia Sharon L R SLR Smith Jennifer A JA

International journal of environmental research and public health 20190828 17

DNA methylation (DNAm) clocks are important biomarkers of cellular aging and are associated with a variety of age-related chronic diseases and all-cause mortality. Examining the relationship between education and lifestyle risk factors for age-related diseases and multiple DNAm clocks can increase the understanding of how risk factors contribute to aging at the cellular level. This study explored the association between education or lifestyle risk factors for age-related diseases and the acceler ...[more]

PMID: 31466396

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Project description:BACKGROUND:Genetic variations in apolipoprotein E (APOE) and proximal genes (PVRL2, TOMM40, and APOC1) are associated with cognitive function and dementia, particularly Alzheimer's disease. Epigenetic mechanisms such as DNA methylation play a central role in the regulation of gene expression. Recent studies have found evidence that DNA methylation may contribute to the pathogenesis of dementia, but its association with cognitive function in populations without dementia remains unclear. METHODS:We assessed DNA methylation levels of 48 CpG sites in the APOE genomic region in peripheral blood leukocytes collected from 289 African Americans (mean age?=?67 years) from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Using linear regression, we examined the relationship between methylation in the APOE genomic region and multiple cognitive measures including learning, memory, processing speed, concentration, language and global cognitive function. RESULTS:We identified eight CpG sites in three genes (PVRL2, TOMM40, and APOE) that showed an inverse association between methylation level and delayed recall, a measure of memory, after adjusting for age and sex (False Discovery Rate q-value?<?0.1). All eight CpGs are located in either CpG islands (CGIs) or CGI shelves, and six of them are in promoter regions. Education and APOE ?4 carrier status significantly modified the effect of methylation in cg08583001 (PVRL2) and cg22024783 (TOMM40), respectively. Together, methylation of the eight CpGs explained an additional 8.7% of the variance in delayed recall, after adjustment for age, sex, education, and APOE ?4 carrier status. Methylation was not significantly associated with any other cognitive measures. CONCLUSIONS:Our results suggest that methylation levels at multiple CpGs in the APOE genomic region are inversely associated with delayed recall during normal cognitive aging, even after accounting for known genetic predictors for cognition. Our findings highlight the important role of epigenetic mechanisms in influencing cognitive performance, and suggest that changes in blood methylation may be an early indicator of individuals at risk for dementia as well as potential targets for intervention in asymptomatic populations.

Project description:BackgroundLow circulating 25-hydroxyvitamin D [25(OH)D] is prevalent in African Americans, but predictors of vitamin D status are understudied compared to Caucasian populations.ObjectiveWe investigated whether certain environmental and genetic factors are predictors of circulating 25(OH)D in 989 elderly African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study.MethodsRegression analysis estimated the cross-sectional association of nongenetic (environmental) factors with 25(OH)D. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D in Caucasian genome-wide association studies (GWASs) were analyzed for association with serum 25(OH)D, including analyses of all imputed SNPs in identified genomic regions. Genome-wide complex trait analysis (GCTA) evaluated the association of all (genome-wide) genotyped SNPs with serum 25(OH)D in the Health ABC Study with replication in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.ResultsGender, study site, season of blood draw, body mass index, dietary supplement use, dairy and cereal consumption, Healthy Eating Index score, and walking >180 min/wk were associated with 25(OH)D (P < 0.05), jointly explaining 25% of the variation in circulating 25(OH)D. Multivitamin supplement use was the strongest predictor of circulating 25(OH)D, and supplement users had a 6.3-μg/L higher serum 25(OH)D concentration compared with nonusers. Previous GWAS-identified gene regions were not replicated in African Americans, but the nonsynonymous rs7041 SNP in group-specific component (vitamin D binding protein) was close to significance thresholds (P = 0.08), and there was evidence for an interaction between this SNP and use of multivitamin supplements in relation to serum 25(OH)D concentration (P = 0.04). Twenty-three percent (95% CI: 0%, 52%) of the variation in serum 25(OH)D was explained by total genetic variation in a pooled GCTA of 2087 Health ABC Study and MESA African-American participants, but population substructure effects could not be separated from other genetic influences.ConclusionsModifiable dietary and lifestyle predictors of serum 25(OH)D were identified in African Americans. GCTA confirms that a proportion of 25(OH)D variability is attributable to genetic variation, but genomic regions associated with the 25(OH)D phenotype identified in prior GWASs of European Americans were not replicated in the Health ABC Study in African Americans.

Dataset Information

Education and Lifestyle Factors Are Associated with DNA Methylation Clocks in Older African Americans.

Publications

Education and Lifestyle Factors Are Associated with DNA Methylation Clocks in Older African Americans.

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