AS534 - Longitudinal study of DNA methylation as a mediator between age and cardiovascular risk

Investigator Names and Contact Information

Karen Conneely (kconnee@emory.edu)

Introduction/Intent

DNA methylation is a potential mediator of age-related risk for cardiovascular disease; such mediation is likely be most powerfully detected through the observation of measured risk factors in the same individuals over time. This study will determine the efficacy of a larger longitudinal study of DNA methylation and cardiovascular risk in WHI individuals participating in the Long Life Study.

Specific Aims

The purpose of this feasibility study is to determine the efficacy of a larger longitudinal study of DNA methylation in the WHI-LLS individuals and facilitate external funding of such a study. If funded, this larger study would represent an expansion of the core scientific resource of the WHI, and could potentially be used by investigators interested in a range of phenotypes and diseases.​

Aim 1: Characterize the relationship between age and DNA methylation at >450,000 CpG sites across the genome for 40 WHI-LLS individuals at three separate timepoints.

Aim 1a) Measure DNA methylation at a third timepoint for the 40 WHI-LLS individuals.

Aim 1b) Construct a methylation-based biomarker for age (DNAm age) and compute age acceleration (DNAm age minus chronological age).

Aim 1c) Fit longitudinal models to assess the non-linear patterns of DNA methylation change with age, both for methylation at individual CpG sites and for DNAm age.

Aim 2: Examine the role of DNA methylation as a mediator between age and CVD risk factors. For each risk factor, fit longitudinal models to assess 1) dependence of risk factor on age, and 2) dependence of risk factor on both age and age acceleration, within the same individuals. Significance of age acceleration in the model will suggest that methylation mediates the relationship between age and the risk factor