An explorative epigenome-wide association study of plasma renin and aldosterone concentration in a Ghanaian population: the RODAM study

Eva L. van der Linden*, Adrienne Halley, Karlijn A.C. Meeks, Felix Chilunga, Charles Hayfron-Benjamin, Andrea Venema, Ingrid M. Garrelds, A. H.Jan Danser, Bert Jan van den Born, Peter Henneman, Charles Agyemang

*Corresponding author for this work

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Abstract

Background: The epigenetic regulation of the renin–angiotensin–aldosterone system (RAAS) potentially plays a role in the pathophysiology underlying the high burden of hypertension in sub-Saharan Africans (SSA). Here we report the first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations and the aldosterone-to-renin ratio (ARR). Methods: Epigenome-wide DNA methylation was measured using the Illumina 450K array on whole blood samples of 68 Ghanaians. Differentially methylated positions (DMPs) were assessed for plasma renin concentration, aldosterone, and ARR using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, hypertension, and technical covariates. Additionally, we extracted methylation loci previously associated with hypertension, kidney function, or that were annotated to RAAS-related genes and associated these with renin and aldosterone concentration. Results: We identified one DMP for renin, ten DMPs for aldosterone, and one DMP associated with ARR. Top DMPs were annotated to the PTPRN2, SKIL, and KCNT1 genes, which have been reported in relation to cardiometabolic risk factors, atherosclerosis, and sodium-potassium handling. Moreover, EWAS loci previously associated with hypertension, kidney function, or RAAS-related genes were also associated with renin, aldosterone, and ARR. Conclusion: In this first EWAS on RAAS hormones, we identified DMPs associated with renin, aldosterone, and ARR in a SSA population. These findings are a first step in understanding the role of DNA methylation in regulation of the RAAS in general and in a SSA population specifically. Replication and translational studies are needed to establish the role of these DMPs in the hypertension burden in SSA populations.

Original languageEnglish
Article number159
JournalClinical Epigenetics
Volume14
Issue number1
DOIs
Publication statusPublished - 1 Dec 2022

Bibliographical note

Funding Information:
The current work was supported by the European Commission under the Framework Programme (grant number: 278901) and European Research Council (grant number: 772244). K.A.C.M. is supported by the Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (1ZIAHG200362). The study funder had no role in the study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all the data and the final responsibility to submit for publication.

Publisher Copyright:
© 2022, The Author(s).

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