# High Dimensional Mediation Analysis for DNA Methylation Markers Mediating Cardiovascular Health Metrics and Cardiovascular Diseases

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $236,222

## Abstract

Recent advances in the study of epigenetics and human diseases have prompted a substantial increase in
research on the extent to which DNA methylation mediates the effects of environmental exposures on health
outcomes. With new and advancing technologies, epigenome-wide DNA methylation data (EWAS) have
become the standard for large, population-based epigenetic studies while simultaneously introducing new
methodological challenges unique to the use of high-dimensional data in mediation analyses. Due to these
challenges, previous studies on epigenetic-mediated effects were generally forced to focus on candidate
(gene-specific) methylation markers. More systematic research into this area will remain stalled until the urgent
need for analytical methods appropriate and specific to EWAS mediation analysis is met.
We propose to develop and apply new analytical approaches to high-dimensional mediation analysis methods
for epigenome-wide DNA methylation studies. We will integrate high-dimensional screening and model
selection methods into the traditional mediation analysis framework. We will also address sophisticated
practical issues in conducting this type of data analysis, specifically: grouping effects of DNA methylation
markers on health outcomes, and the generally high correlation among methylation markers. Finally, we will
compile and disseminate a user-friendly software package to facilitate implementation of the proposed
methods.
We will test our proposed methods using data from the Coronary Artery Risk Development in Young Adults
Study (CARDIA), a large longitudinal study with available EWAS data that examines the risk factors,
development, and determinants of clinical and subclinical cardiovascular disease. Our discoveries may lead to
new insights into the mechanisms by which DNA methylation mediates the effects of environmental exposures
on health outcomes. It may also inform the development of new interventions targeting these methylation
markers and improving the prevention and treatment of disease.

## Key facts

- **NIH application ID:** 9918838
- **Project number:** 5R21AG063370-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lifang Hou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $236,222
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918838

## Citation

> US National Institutes of Health, RePORTER application 9918838, High Dimensional Mediation Analysis for DNA Methylation Markers Mediating Cardiovascular Health Metrics and Cardiovascular Diseases (5R21AG063370-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9918838. Licensed CC0.

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