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Journal article
DNA Methylation Mediates the Association Between Individual and Neighborhood Social Disadvantage and Cardiovascular Risk Factors
Frontiers in cardiovascular medicine, v 9, pp 848768-848768
2022
PMID: 35665255
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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
< 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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Details
- Title
- DNA Methylation Mediates the Association Between Individual and Neighborhood Social Disadvantage and Cardiovascular Risk Factors
- Creators
- Yi Zhe Wang - University of Michigan–Ann ArborWei Zhao - University of Michigan–Ann ArborFarah Ammous - University of Michigan–Ann ArborYanyi Song - University of Michigan–Ann ArborJiacong Du - University of Michigan–Ann ArborLulu Shang - University of Michigan–Ann ArborScott M Ratliff - University of Michigan–Ann ArborKari Moore - Drexel UniversityKristen M Kelly - University of Michigan–Ann ArborBelinda L Needham - University of Michigan–Ann ArborAna V Diez Roux - Drexel UniversityYongmei Liu - Duke UniversityKenneth R Butler - University of Mississippi Medical CenterSharon L R Kardia - University of Michigan–Ann ArborBhramar Mukherjee - University of Michigan–Ann ArborXiang Zhou - University of Michigan–Ann ArborJennifer A Smith - University of Michigan–Ann Arbor
- Publication Details
- Frontiers in cardiovascular medicine, v 9, pp 848768-848768
- Publisher
- Frontiers
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Urban Health Collaborative
- Web of Science ID
- WOS:000805629500001
- Scopus ID
- 2-s2.0-85138517368
- Other Identifier
- 991019168722204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems