# Association analysis between an epigenetic risk score and blood pressure

## TL;DR

This study shows that an epigenetic score based on alcohol-related DNA changes is linked to higher blood pressure in thousands of people.

## Contribution

The novel contribution is demonstrating that an alcohol consumption epigenetic risk score is associated with blood pressure traits in multiple cohorts.

## Key findings

- A one-unit increase in the epigenetic risk score was associated with 1.93 mm Hg higher systolic blood pressure in the Framingham Heart Study.
- Meta-analysis across eight external cohorts confirmed a 0.74 mm Hg higher systolic blood pressure per ERS unit.
- Longitudinal analyses found no association between baseline ERS and future blood pressure changes or new hypertension cases.

## Abstract

Epigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases.

We generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day (p < 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 (p = 0.002) and 0.50 (p = 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN.

Our findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.