# Association of DNA methylation with hypertension and blood pressure: a 7-year longitudinal study from KORA F4/FF4

## TL;DR

This study found new DNA methylation sites linked to blood pressure and long-term hypertension, suggesting a dynamic role for epigenetics in blood pressure regulation.

## Contribution

The study identifies novel CpG sites associated with blood pressure and persistent hypertension through a 7-year longitudinal analysis.

## Key findings

- One CpG site was associated with systolic blood pressure and four with diastolic blood pressure, including novel loci like RILP and SVIL.
- Differential annual methylation changes were observed for 23 CpG sites linked to diastolic blood pressure, highlighting genes such as RHPN2 and ZNF69.
- Twenty CpG sites were associated with persistent hypertension, including PLCB2 and MPPE1, with some correlating to gene expression in whole blood.

## Abstract

Hypertension (HTN) has been linked to changes in DNA methylation. However, longitudinal epigenome-wide analyses are still limited.

We analyzed data from the KORA F4 and FF4 studies, conducted approximately 7 years apart. The dataset included 2614 participants, each with DNA methylation measured at least once. Leucocyte DNA methylation was profiled using the Illumina 450 k and EPIC arrays. Linear mixed-effects models were employed to identify associations between methylation sites and HTN status, systolic (SBP) and diastolic blood pressure (DBP). Interaction terms with follow-up time captured longitudinal methylation trajectories. We further examined CpG sites related to reversed, persistent, or progressive HTN and assessed their correlations with gene expression.

One CpG site was associated with SBP and four with DBP, all representing novel loci, including RILP (cg08625564) and SVIL (cg15298791). Differential annual methylation changes were observed for 2, 23, and 12 CpG sites by HTN status, SBP, and DBP, respectively, highlighting genes such as RHPN2, CLDND1, ZNF69, and FKBP1B. Twenty CpG sites were associated with persistent HTN, including PLCB2 and MPPE1. In whole blood, 22 significant CpG–transcript pairs were detected, involving 14 CpG sites and 19 gene transcripts.

This longitudinal epigenome-wide study identified novel CpG sites associated with blood pressure and persistent HTN. We observed differential DNA methylation trajectories over time linked to HTN, SBP, and DBP, with several changes correlating with gene expression, suggesting functional relevance. These findings underscore the dynamic role of DNA methylation in blood pressure regulation and provide new insights into epigenetic mechanisms of HTN.

The online version contains supplementary material available at 10.1186/s12916-026-04672-8.