Role of DNA methylation on the association between physical activity and cardiovascular diseases: results from the longitudinal multi-ethnic study of atherosclerosis (MESA) cohort

Hangchuan Shi,Jingzhong Ding,Yongmei Liu,Dongmei Li,Deborah J Ossip,Nicole L Mayo,Wendy S Post,Robert C Block,Daniel A Lopez,Ina Hoeschele,Chen Yan,Alain G Bertoni,Zidian Xie,Si Chen

doi:10.1186/s12864-021-08108-w

Abstract

BackgroundThe complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study. We examined the role of DNA methylation on the association between PA and CVD.ResultsThe Multi-Ethnic Study of Atherosclerosis (MESA) cohort Exam 5 data with 1065 participants free of CVD were used for final analysis. The quartile categorical total PA variable was created by activity intensity (METs/week). During a median follow-up of 4.0 years, 69 participants developed CVD. Illumina HumanMethylation450 BeadChip was used to provide genome-wide DNA methylation profiles in purified human monocytes (CD14+). We identified 23 candidate DNA methylation loci to be associated with both PA and CVD. We used the structural equation modeling (SEM) approach to test the complex relationships among multiple variables and the roles of mediators. Three of the 23 identified loci (corresponding to genes VPS13D, PIK3CD and VPS45) remained as significant mediators in the final SEM model along with other covariates. Bridged by the three genes, the 2nd PA quartile (β = − 0.959; 95%CI: − 1.554 to − 0.449) and the 3rd PA quartile (β = − 0.944; 95%CI: − 1.628 to − 0.413) showed the greatest inverse associations with CVD development, while the 4th PA quartile had a relatively weaker inverse association (β = − 0.355; 95%CI: − 0.713 to − 0.124).ConclusionsThe current study is among the first to simultaneously examine the relationships among PA, DNA methylation, and CVD in a large cohort with long-term exposure. We identified three DNA methylation loci bridged the association between PA and CVD. The function of the identified genes warrants further investigation in the pathogenesis of CVD.

Highlights

The complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study
We identified three DNA methylation loci bridged the association between PA and CVD
We evaluated the role of DNA methylation on the longitudinal association between PA and CVD, along with other covariates, using data from the MultiEthnic Study of Atherosclerosis (MESA)

Summary

Introduction

The complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study. We examined the role of DNA methylation on the association between PA and CVD. Cardiovascular disease (CVD) is the leading cause of mortality in the United States [1]. The etiology of CVD involves complex multifactorial mechanisms including environmental and genetic factors [3]. Among the environmental or behavioral exposures, physical activity (PA) has consistently been shown in epidemiological studies to be associated with reduced risk of CVD [4]. Owing to the evolutionary development of genomic study methods, recent studies suggest that epigenetic modifications are involved in the association between PA and CVD [6]

Methods

Results

Conclusion