Low socioeconomic status (SES) and living in a disadvantaged neighborhood are associated with poor cardiovascular health. Multiple lines of evidence have linked DNA methylation to both cardiovascular risk factors and social disadvantage indicators. However, limited research has investigated the role of DNA methylation in mediating the associations of individual- and neighborhood-level disadvantage with multiple cardiovascular risk factors in large, multi-ethnic, population-based cohorts. We examined whether disadvantage at the individual level (childhood and adult SES) and neighborhood level (summary neighborhood SES as assessed by Census data and social environment as assessed by perceptions of aesthetic quality, safety, and social cohesion) were associated with 11 cardiovascular risk factors including measures of obesity, diabetes, lipids, and hypertension in 1,154 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). For significant associations, we conducted epigenome-wide mediation analysis to identify methylation sites mediating the relationship between individual/neighborhood disadvantage and cardiovascular risk factors using the JT-Comp method that assesses sparse mediation effects under a composite null hypothesis. In models adjusting for age, sex, race/ethnicity, smoking, medication use, and genetic principal components of ancestry, epigenetic mediation was detected for the associations of adult SES with body mass index (BMI), insulin, and high-density lipoprotein cholesterol (HDL-C), as well as for the association between neighborhood socioeconomic disadvantage and HDL-C at FDR
- Award ID(s):
- 1739805
- NSF-PAR ID:
- 10234897
- Date Published:
- Journal Name:
- International Journal of Molecular Sciences
- Volume:
- 22
- Issue:
- 7
- ISSN:
- 1422-0067
- Page Range / eLocation ID:
- 3717
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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q < 0.05. The 410 CpG mediators identified for the SES-BMI association were enriched for CpGs associated with gene expression (expression quantitative trait methylation loci, or eQTMs), and corresponding genes were enriched in antigen processing and presentation pathways. For cardiovascular risk factors other than BMI, most of the epigenetic mediators lost significance after controlling for BMI. However, 43 methylation sites showed evidence of mediating the neighborhood socioeconomic disadvantage and HDL-C association after BMI adjustment. The identified mediators were enriched for eQTMs, and corresponding genes were enriched in inflammatory and apoptotic pathways. Our findings support the hypothesis that DNA methylation acts as a mediator between individual- and neighborhood-level disadvantage and cardiovascular risk factors, and shed light on the potential underlying epigenetic pathways. Future studies are needed to fully elucidate the biological mechanisms that link social disadvantage to poor cardiovascular health. -
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Abstract DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how stress factors impact aging. Deer mice (
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Abstract Objectives Bomb pulse (BP) radiocarbon (14C) dating methods are used by forensic anthropologists to estimate the year‐of‐death (YOD) of unidentified individuals. Method resolution and accuracy depend on establishing lag times, or the difference between a tissue's BP14C‐derived year and the YOD, of various tissue types from known deceased persons. Bone lag times span many years and are thought to increase with age as a function of slowing remodeling rates. However, remodeling rates for various skeletal elements, bone structures and phases are not well known.
Materials and Methods Here a simple method is used to estimate bone remodeling rates from a compilation of published cortical femur bone collagen BP14C measurements (
n = 102). Linear regression models and nonparametric tests are used to detect changes in lag times and remodeling rates with increasing age‐at‐death.Results Remodeling rates and lag times of 3.5%/year and 29 years, respectively, are estimated from individuals aged 40–97 years. In contrast to previous work, the analysis yielded modest and negligible changes in remodeling rates and lag times with advancing age. Moreover, statistically significant differences in remodeling rates and lag times were not found between reported females and males.
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Abstract Background and objectives The Developmental Origins of Health and Disease hypothesis posits that early life adversity is associated with poor adult health outcomes. Epidemiological evidence has supported this framework by linking low birthweight with adult health and mortality, but the mechanisms remain unclear. Accelerated epigenetic aging may be a pathway to connect early life experiences with adult health outcomes, based on associations of accelerated epigenetic aging with increased morbidity and mortality.
Methodology Sixty-seven mother-infant dyads were recruited in the eastern Democratic Republic of Congo. Birthweight data were collected at birth, and blood samples were collected at birth and follow-up visits up to age 3. DNA methylation data were generated with the Illumina MethylationEPIC array and used to estimate epigenetic age. A multilevel model was used to test for associations between birthweight and epigenetic age acceleration.
Results Chronological age was highly correlated with epigenetic age from birth to age 3 (r = 0.95, p < 2.2 × 10−16). Variation in epigenetic age acceleration increased over time. Birthweight, dichotomized around 2500 g, predicted epigenetic age acceleration over the first 3 years of life (b = −0.39, p = 0.005).
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/ijms22073717
