Epigenome-wide association study of physical activity and physiological parameters in discordant monozygotic twins

Sep 20, 2026

Uploaded by Patrick

An epigenome-wide association study (EWAS) analyzed buccal cells from monozygotic twins reared together in childhood but living apart as adults to test links between neighborhood walkability and objectively measured physical activity. Male and female twin pairs were analyzed separately due to epigenetic sex differences. Differential DNA methylation regions were compared for pairs discordant in body mass index, physical activity, and walkability, and weighted gene coexpression network analysis was used to associate methylation sites with physiological traits. Physical-activity discordant pairs showed methylation changes correlated with reduced metabolic parameters, involving more than fifty genes previously tied to vigorous activity and metabolic risk factors, supporting systemic epigenetic effects on obesity etiology.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Background and rationale

Built environment and physical activity

Epigenetics and obesity etiology

Study design and analyses

Twin cohorts and discordant phenotypes

EWAS and sex-stratified differential methylation

WGCNA for trait-linked sites

Key findings and implications

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Epigenome‑wide association study of physical activity and physiological parameters in discordant monozygotic twins Glen E. Duncan1, Ally Avery1, Jennifer L. M. Thorson2, Eric E. Nilsson2, Daniel Beck2 & Michael K. Skinner2* An epigenome‑wide association study (EWAS) was performed on buccal cells from monozygotic‑twins (MZ) reared together as children, but who live apart as adults. Cohorts oftwin pairs were used to investigate associations between neighborhood walkability and objectively measured physical activity (PA) levels. Due to dramatic cellular epigenetic sex differences, male and female MZ twin pairs were analyzed separately to identify differential DNA methylation regions (DMRs). A priori comparisons were made on MZ twin pairs discordant on body mass index (BMI), PA levels, and neighborhood walkability. In addition to direct comparative analysis to identify specific DMRs, a weighted genome coexpression network analysis (WGCNA) was performed to identify DNA methylation sites associated with the physiological traits of interest. The pairs discordant in PA levels had epigenetic alterations that correlated with reduced metabolic parameters (i.e., BMI and waist circumference). The DNA methylation sites are associated with over fifty genes previously found to be specific to vigorous PA, metabolic risk factors, and sex. Combined observations demonstrate that behavioral factors, such as physical activity, appear to promote systemic epigenetic alterations that impact metabolic risk factors. The epigenetic DNA methylation sites and associated genes identified provide insight into PA impacts on metabolic parameters and the etiology of obesity. Abbreviations EWAS MZ PA DMRs BMI WGCNA BE GWASMeDIP MeDIP-Seq PCA MVPA WSTR Epigenome-wide association study Monozygotic twins Physical activity DNA methylation regions Body mass index Weighted genome complex network analysis“Built” environment Genome-wide association studies Methylated DNA immunoprecipitation Next generation sequencing Principal component analysis Minutes of moderate to vigorous physical activity Washington State Twin Registry Regular physical activity (PA) and proper nutrition are the foundations of chronic disease prevention and treatment efforts. However, we have failed to motivate adoption and maintenance of these critical health behaviorsat the population level. Strategies to increase levels of PA in the population are a critical public health goal1–4. The role of the “built” environment in supporting health behaviors has received increased attention over the last decade because of the failure of individual-level approaches (i.e., behavior change) to impact this population-level problem (i.e., obesity and associated metabolic syndrome).“Healthy” or “walkable” built environments provide 1Department of Nutrition and Exercise Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA. 2Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA.* email: [skinner@wsu.edu](skinner@wsu.edu) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) opportunities for PA and better choices for food. These environments potentially lead to lower obesity and associated diseases5. Detrimental built environments include sprawling suburbs where automobiles are the only transportation option and fast-food restaurants and strip malls are numerous. This “obesogenic” environment minimizes energy expenditure and maximizes energy intake to promote obesity. While it is known that exposure to an obesogenic built environment negatively influences PA and eating behaviors, it is not clear whether exposure to an obesogenic built environment can affect on a molecular level gene activity6. These “molecular signatures” of obesity can be investigated th

FAQs

What cohorts and biological samples were used for the epigenome-wide association study?

The study used buccal cells from monozygotic twin pairs reared together as children, but living apart as adults. Male and female pairs were analyzed separately.

How were discordant twins defined in relation to the exposures and traits?

Twin pairs were discordant on body mass index (BMI), physical activity levels, and neighborhood walkability, enabling comparisons of differential DNA methylation regions.

What relationship did the study find between physical activity differences and metabolic parameters?

Pairs discordant in physical activity showed epigenetic alterations correlated with reduced metabolic parameters, including BMI and waist circumference, supported by methylation sites linked to multiple genes.

Sep 20, 2026

Uploaded by Patrick