Asian-led epigenome study uncovers new DNA methylation markers of artery wall thickness

Carotid intima-media thickness (cIMT), a measure of the inner walls of the neck arteries that predicts cardiovascular events, has gained a set of new epigenetic markers thanks to a study centered on Asian participants. An epigenome-wide association study (EWAS) published in Clinical Epigenetics scanned roughly 850,000 CpG sites across the genome in peripheral blood DNA and identified three novel CpG–cIMT associations, reaching a significance threshold of P < 9.35E−07.

The authors note that cardiovascular disease research has remained Eurocentric despite etiological differences across ancestries, and that Asian populations carry a substantial cardiovascular disease burden with distinct etiological profiles, making them valuable for understanding the biology of subclinical processes linked to cIMT.

These analyses pointed to the CpG site cg08227773: the evidence was compatible with a shared genetic signal linking this site separately to coronary artery disease risk (PSMR = 2.91E−05, coloc PP.H4 = 0.91) and to expression of NBEAL2 (Neurobeachin-like 2), a gene implicated in immune dysregulation (PSMR = 9.13E−08, coloc PP.H4 = 0.69). The authors describe this locus as a candidate for further mechanistic investigation rather than a proven causal mechanism.

An exploratory methylation risk score (MRS) built from the three sentinel CpGs was associated with elevated cIMT in an internal HELIOS evaluation, defined as cIMT at or above the 75th percentile for age, sex and ethnicity. Participants in the top quartile of the score had an Odds Ratio of 2.75 for elevated cIMT compared with the bottom quartile (95% CI 1.47–5.13). The authors frame this MRS as exploratory, and the score’s performance was assessed within the same cohort rather than in an independent external population.

As an open-access paper published on 28 September 2026 and shared early as a citable accepted-manuscript version subject to further edits, the study positions Asian-led discovery as a route to broader representation in cardiovascular epigenetics. Its conclusions are measured: three novel DNA methylation markers for cIMT that collectively track elevated cIMT burden in an exploratory analysis, and one locus, cg08227773–NBEAL2, nominated through shared genetic signals for coronary artery disease risk and gene expression as a priority for future mechanistic work.

Subject of Research: DNA methylation markers for carotid intima-media thickness identified in an Asian cohort

Article Title: Epigenome-wide association study in Asian cohort identifies novel DNA methylation markers for carotid intima-media thickness

Article References: Tan, K., Harris, S. E., Maddock, J., Tay, D., Jain, P. R., The HELIOS Study Team, Bahai, A., Lam, B., Low, D., Riboli, E., Wansaicheong, G., Sanikini, H., Ng, H. K., Lee, J., Ngeow, J., Li, K., Tsilidis, K., Sadhu, N., Elliott, P., … Loh, M. (2026). Epigenome-wide association study in Asian cohort identifies novel DNA methylation markers for carotid intima-media thickness. Clinical Epigenetics. https://doi.org/10.1186/s13148-026-02245-3

Image Credits: AI Generated

DOI: 10.1186/s13148-026-02245-3

Keywords: DNA methylation, carotid intima-media thickness, EWAS, cardiovascular disease, Asian cohort, coronary artery disease, NBEAL2, methylation risk score, Mendelian randomisation, colocalisation, HELIOS cohort, epigenetics