Physical Activity and Genome-wide DNA Methylation: The REgistre GIroní del COR Study
- 1 March 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Medicine & Science in Sports & Exercise
- Vol. 52 (3), 589-597
- https://doi.org/10.1249/mss.0000000000002174
Abstract
Introduction DNA methylation may be one of the biological mechanisms underlying the health benefits of physical activity (PA). Our objective was to determine the association between PA and genome-wide DNA methylation at CpG level. Methods We designed a two-stage epigenome wide association study. In the discovery stage, we used 619 individuals from the REgistre GIroní del COR cohort. Next, we validated the CpG suggestively associated with PA (P < 10−5) in two independent populations (n = 1735 and 190, respectively). Physical activity was assessed with validated questionnaires and classified as light PA (LPA), moderate PA, vigorous PA, moderate-vigorous PA (MVPA) and total PA. We examined linear and nonlinear associations and meta-analyzed the results in the three populations. The linear associations were meta-analyzed with a fixed-effects model and the P values of the nonlinear associations with the Stouffer and Fisher methods. We established a P value threshold that fulfilled Bonferroni criteria over the number of CpG analyzed (0.05/421,940 = 1.185 × 10−7). Results In the meta-analyses, two CpG sites had a statistically significant nonlinear association with MVPA. cg24155427 (P = 1.19 × 10−9), located in an intergenic region in chromosome 1, has been previously associated with smoking, lupus, and aging. cg09565397 (P = 1.59 × 10−7), located within DGAT1 in chromosome 8, which encodes an enzyme involved in triacylglycerol synthesis. Conclusions This population-based study identified two new, differentially methylated CpG sites with a nonlinear dose–response relationship to MVPA. These associations must be additionally validated and may be considered for further research on the biological mechanisms underlying health benefits of PA.This publication has 45 references indexed in Scilit:
- A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose TissuePLoS Genetics, 2013
- Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancyThe Lancet, 2012
- White blood cell global methylation and IL-6 promoter methylation in association with diet and lifestyle risk factors in a cancer-free populationEpigenetics, 2012
- DNA methylation arrays as surrogate measures of cell mixture distributionBMC Bioinformatics, 2012
- The sva package for removing batch effects and other unwanted variation in high-throughput experimentsBioinformatics, 2012
- Dose Response Between Physical Activity and Risk of Coronary Heart DiseaseCirculation, 2011
- Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysisBMC Bioinformatics, 2010
- Epigenetics as a unifying principle in the aetiology of complex traits and diseasesNature, 2010
- Exercise Effects on Methylation ofASCGeneInternational Journal of Sports Medicine, 2010
- A questionnaire for the assessment of leisure time physical activitiesJournal of Chronic Diseases, 1978