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[Preprint]. 2024 Apr 19:rs.3.rs-4243866.
doi: 10.21203/rs.3.rs-4243866/v1.

Association analysis between an epigenetic risk score and blood pressure

Helena Bui  1 , Amena Keshawarz  1 , Mengyao Wang  2 , Mikyeong Lee  3 , Scott M Ratliff  4 , Lisha Lin  4 , Kira S Birditt  4 , Jessica D Faul  4 , Annette Peters  5 , Christian Gieger  6 , Thomas Delerue  5 , Sharon L R Kardia  4 , Wei Zhao  4 , Xiuqing Guo  7 , Jie Yao  7 , Jerome I Rotter  7 , Yi Li  2 , Xue Liu  2 , Dan Liu  8 , Juliana F Tavares  8 , Gökhan Pehlivan  8 , Monique M B Breteler  8 , Irma Karabegovic  9 , Carolina Ochoa-Rosales  9 , Trudy Voortman  9 , Mohsen Ghanbari  9 , Joyce B J van Meurs  9 , Mohamed Kamal Nasr  10 , Marcus Dörr  11 , Hans J Grabe  10 , Stephanie J London  3 , Alexander Teumer  10 , Melanie Waldenberger  6 , David R Weir  4 , Jennifer A Smith  4 , Daniel Levy  1 , Jiantao Ma  12 , Chunyu Liu  13
Affiliations

Association analysis between an epigenetic risk score and blood pressure

Helena Bui et al. Res Sq. .

Abstract

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

Results: 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.

Conclusions: 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.

Keywords: DNA methylation; alcohol; blood pressure; epigenetic risk score; hypertension.

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Conflict of interest statement

Competing Interests All first and corresponding authors of this manuscript have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Meta-analysis of cross-sectional association analyses of ERS in relation to systolic blood pressure in eight independent external cohorts (n = 11,544). ALHS, Agricultural Lung Health Study; GENOA, Genetic Epidemiology Network of Arteriopathy; HRS, Health and Retirement Study; KORA, Cooperative Health Research in the Region Augsburg; MESA, Multi-Ethnic Study of Atherosclerosis; SHIP, Study of Health in Pomerania; FE, Fixed Effect; 95% CI, Confidence Interval.
Figure 3
Figure 3
Cross-sectional meta-analysis of ERS in relation to diastolic blood pressure in eight independent external cohorts (n = 11,544). ALHS, Agricultural Lung Health Study; GENOA, Genetic Epidemiology Network of Arteriopathy; HRS, Health and Retirement Study; KORA, Cooperative Health Research in the Region Augsburg; MESA, Multi-Ethnic Study of Atherosclerosis; SHIP, Study of Health in Pomerania; FE, Fixed Effect; 95% CI, Confidence Interval.
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