Effects of race and socioeconomic status on the epigenetic aging clock

种族和社会经济地位对表观遗传衰老时钟的影响

• 批准号: 10473355
• 负责人: michele k evans
• 金额: $ 47.81万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10473355
• 关键词: Acceleration; Address; Adult; Affect; African American; Age; Aging; Animal Model; Area; Behavioral; Biological; Blood; Cardiovascular Diseases; Chronology; Cognition; Cognitive; CpG dinucleotide; Cytosine; DNA; DNA Methylation; Data; Data Analyses; Demographic Factors; Development; Discrimination; Disease; Education; Elderly; Environmental Exposure; Epigenetic Process; European; Female; Future; GSTT1 gene; Gene Expression Regulation; Genes; Genetic; Genomics; Glutathione S-Transferase; Growth and Development function; Guidelines; Health; Human; Individual; Lead; Linear Regressions; Liver; Longevity; Longitudinal Studies; Malignant Neoplasms; Measurement; Measures; Metabolic syndrome; Methods; Methylation; Mitochondria; Modeling; Neighborhoods; Obesity; Outcome; Participant; Pathway interactions; Peptide Hydrolases; Peripheral Blood Mononuclear Cell; Phenotype; Play; Population; Positioning Attribute; Poverty; Process; Protein phosphatase; Psychosocial Stress; Publications; Quality Control; Race; Residual state; Risk; Risk Factors; Role; Sample Size; Sampling; Site; Socioeconomic Status; Specific qualifier value; Stearoyl-CoA Desaturase; TXNIP gene; Time; Tissues; Whole Blood; Woman; age related; base; bead chip; bisulfite; cardiometabolic risk; caucasian American; cell type; cohort; depressive symptoms; design; differential expression; epidemiology study; epigenome-wide association studies; epigenomics; fitness; genome wide methylation; genome-wide; health care availability; health disparity; healthy aging; human model; insight; lifestyle factors; male; men; methylation pattern; middle age; mortality; novel; peripheral blood; premature; sex; social health determinants

We designed a sub-cohort of individuals from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study that would enable us to address the effects of race and SES on DNAm age. Based on power and sample size calculations, and extensive discussions with our collaborative team, we have selected 508 participants from Wave 1 of HANDLS. We chose these individuals with peripheral blood DNA samples from both Wave 1 and Wave 3, which will allow us to perform longitudinal study of accelerated DNAm age. These individuals were comprised of above and below poverty, AA and white, male and female across the age-span of the HANDLS study (30-64 yrs.). We measured genome-wide DNA methylation (866,836 CpGs) using the Illumina MethylationEPIC BeadChip in blood DNA extracted from 487 middle-aged AA (N=244) and white (N=243), men (N=248) and women (N=239). The mean (sd) age was 48.4 (8.8) in AA and 49.0 (8.7) in whites (p=0.48). We identified 4,930 significantly associated aDMPs in AAs and 469 in whites. Of these, 75.6% and 53.1% were novel, largely driven by the increased number of measured CpGs in the EPIC array, in AA and whites, respectively. AAs had more age-associated DNAm changes than whites in genes implicated in age-related diseases and cellular pathways involved in growth and development. We assessed three epigenetic age acceleration measures (universal, intrinsic and extrinsic). AAs had a significantly slower extrinsic aging compared to whites. Furthermore, compared to AA women, both AA and white men had faster aging in the universal age acceleration measure (+2.04 and +1.24 years, respectively, p<0.05). AAs have more wide-spread methylation changes than whites. Race and sex interact to underlie biological age acceleration suggesting altered DNA methylation patterns may be important in age-associated health disparities. In future, we will also analyze genome-wide DNA methylation longitudinally using DNA samples from wave 3. Once the wave 3 methylation measurement is complete, we will follow similar quality control standards, and perform longitudinal data analysis using linear mixed-effects regression models (i) to assess the effect of sex, race, SES, and their interaction on the longitudinal changes of epigenetic age acceleration; and (ii) to identify age-associated differentially methylated CpG sites and differentially methylated regions that change longitudinally. We will also perform genome-wide methylation analysis on the longitudinal data to identify differentially methylated CpG positions and regions associated with age to identify genes that could play role in the aging processes and pathways. Data generated will help to understand factors affecting the longitudinal changes in epigenetic age acceleration as well as in genome-wide CpG methylation. We also have examined an important area of health disparities, metabolic syndrome. Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors for all-cause mortality, cardiovascular disease, and cancer. Identifying epigenetic alterations associated with MetS in African Americans (AAs) and Whites may provide insight into genes that influence its differential health outcomes. We examined DNA methylation (DNAm) and performed an epigenome-wide association study (EWAS) of MetS among AAs and Whites with and without MetS. We assessed age, race and poverty status associated DNAm among AAs (n = 225) and White (n = 233) adults using NCEP-ATP III guidelines. Genome-wide DNAm measurement was assessed using Illumina Infinium Methylation EPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) were identified using dmpFinder and bumphunter. EWAS was performed using CpGassoc. We found significant DMPs associated with age, poverty status and MetS in each race. GSTT1(Glutathione S-Transferase Theta 1) was one of the top-hypermethylated genes and MIPEP (Mitochondrial Intermediate Peptidase) was one of the most hypomethylated genes when comparing AAs with and without MetS. PPP1R13L (Protein Phosphatase 1 Regulatory Subunit 13 Like) was the top hypermethylated and SCD (stearoyl-CoA desaturase-1) was one of the most hypomethylated genes for Whites with and without MetS. EWAS results showed that DNAm differences might contribute to MetS risk among Whites and AAs since different genes were identified in AAs and Whites. We replicated previously identified MetS associated genes and found that Thioredoxin-interacting protein (TXN1P) was statistically significantly differentially expressed only in Whites. Our results may be useful in further studies of genes underlying differences in MetS among AAs and Whites. We have also begun to examine the relationships between epigenetic age acceleration and important behavioral conditions relevant to health disparities and aging; these include depressive symptoms, perceived discrimination and cognition.

我们设计了一个亚队列的个体从健康老龄化的多样性社区在整个生命周期（HANDLS）研究，这将使我们能够解决种族和社会经济地位对DNAm年龄的影响。基于功率和样本量计算，以及与合作团队的广泛讨论，我们从HANDLS的第一批中选择了508名参与者。我们选择了这些具有第1波和第3波外周血DNA样本的个体，这将使我们能够对加速的DNA年龄进行纵向研究。在HANDLS研究的年龄跨度（30-64岁）中，这些个体包括贫困以上和贫困以下的人、嗜酒者和白人、男性和女性。