A PROOF-OF-PRINCIPLE EPIGENOME-WIDE ASSOCIATION STUDY OF PLASMA RENIN AND ALDOSTERONE CONCENTRATION IN A GHANAIAN POPULATION: THE RODAM STUDY

Abstract

Objective: 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). In this first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations, we explored the association between DNA methylation and concentrations of renin and aldosterone. Design and method: Epigenome-wide DNA methylation was measured using the Illumina 450k array on whole blood samples of 68 Ghanaian participants of the Research on Obesity and Diabetes among African Migrants Study (RODAM). Differentially methylated positions (DMPs) were assessed for plasma renin and aldosterone concentration 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 epigenome-wide significant DMP associated with renin, and ten DMPs associated with aldosterone. 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 and aldosterone concentration. Conclusions: In this first EWAS on RAAS hormones, we identified DMPs associated with renin and aldosterone 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. The results of this proof-of-principle study will inform new analyses including a larger sample size and a new methylation array (Illumina Infinium MethylationEPIC), which will we use to replicate these initial findings. This will help to further establish the role of DNA methylation and the RAAS system in the hypertension burden in SSA populations.