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Med Sci Sports Exerc. 2020 Mar;52(3):589-597. doi: 10.1249/MSS.0000000000002174.

Physical Activity and Genome-wide DNA Methylation: The REgistre GIroní del COR Study.

Author information

1
Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Catalonia, SPAIN.
2
Pompeu Fabra University (UPF), Barcelona, Catalonia, SPAIN.
3
CIBER Cardiovascular Diseases (CIBERCV), SPAIN.
4
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, SPAIN.
5
CIBER Cancer (CIBERONC), SPAIN.
6
Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Catalonia, SPAIN.
7
Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, SPAIN.
8
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, SPAIN.
9
CIBER Epidemiology and Public Health (CIBERESP), SPAIN.
10
Medical School, Universidad de Concepción, Concepción, CHILE.
11
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.
12
Medicine Department, Medical School, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Catalonia, SPAIN.

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) 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).

RESULTS:

In the meta-analyses, two CpG sites had a statistically significant nonlinear association with MVPA. cg24155427 (P = 1.19 × 10), located in an intergenic region in chromosome 1, has been previously associated with smoking, lupus, and aging. cg09565397 (P = 1.59 × 10), 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.

PMID:
31652233
PMCID:
PMC7023998
[Available on 2021-03-01]
DOI:
10.1249/MSS.0000000000002174

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