Leisure-time physical activity and cardiovascular disease risk assessed via epigenetic surrogate scores for plasma proteins and metabolites

Low levels of leisure-time physical activity (LTPA) are linked to adverse health outcomes, including increased cardiovascular disease (CVD) risk. Circulating plasma proteins and metabolites can provide early insights into disease processes and may help predict future risk before clinically detectable symptoms or irreversible pathological changes occur. Recent advances enable the estimation of epigenetic surrogate scores from blood DNA methylation (DNAm) for specific proteins, metabolites, and chronic inflammation. These DNAm-based scores are cost-effective and highly reproducible, offering a promising approach for large-scale cohort studies when DNAm data are available.

This project will evaluate the validity of epigenetic surrogate scores for CVD-related plasma proteins and metabolites and assess whether these scores capture genetic and environmental influences shared with directly measured biomarkers. We will further examine whether epigenetic score profiles differ by LTPA level and clarify the role of body mass index (BMI) as a confounder, moderator, or mediator in these associations. Moreover, we aim to triangulate evidence across multiple study designs to assess whether the associations between LTPA and specific CVD-related epigenetic scores are causal.

Funding
The Finnish Foundation for Cardiovascular Research (2026)

Research group
Vastuullinen tutkija
Anna Kankaanpää, Postdoctoral Researcher, Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä

Elina Sillanpää, Associate Professor, Faculty of Sport and Health Sciences, University of Jyväskylä

Collaborators
Miina Ollikainen, Senior Researcher, Minerva Foundation Institute for Medical Research; Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Sari Aaltonen, Senior Researcher, Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Ulf Ekelund, Professor, Norwegian School of Sport Sciences