Abstract P111: Differentially Methylated DNA Regions In Left Ventricular Hypertrophy: A HyperGEN Study

Abstract

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality that is commonly associated with hypertension. African Americans (AAs) experience an especially high risk of LVH. Genomic studies have identified potential candidate genes associated with LVH, but more research is needed to further explain the high estimated heritability for these traits in AAs. Epigenetic modifications, such as DNA methylation, may account for the unexplained heritability in LVH in AAs. In this study, we used epigenotype and echocardiography data from 636 African Americans selected from the Hypertension Genetic Epidemiology Network (HyperGEN) to identify differentially methylated regions (DMRs) of DNA in association with LV related traits. DNA was isolated from participants’ whole blood, and more than 485,000 CpGs were assayed on Illumina Methyl450K arrays. Linear mixed models were used to test the association between a DMR and LV trait using the coMethDMR package in R. We identified several DMRs associated with LV traits in HyperGEN. There was an association between methylation of XKR6 and ejection fraction (β[SE]:0.005[0.001], FDR: 0.056), as well as TRAK1 and LV internal diastolic dimension (β[SE]:0.113[0.027], FDR: 0.042). There was also an inverse relationship between LV mass indexed to height and methylation of GSE1 (β[SE]:-0.002[0.001], FDR: 0.085), RPS15A (β[SE]:-0.002[0.001], FDR: 0.085), and PSMD7 (β[SE]:-0.003[0.001], FDR: 0.085). Additionally, relative wall thickness was inversely associated with a DMR annotated to DNHD1 (β[SE]:-1.269[0.275], FDR: 0.008). Methylation variations of GSE1 , PSMD7 , and DNHD1 have previously been linked to cardiac structural function, and external validation of these findings is in progress. In summary, differentially methylated regions of DNA may help explain additional variation in LVH-related traits and heritability in AAs. Future studies should evaluate potential relationships between regional DNA methylation patterns and the development and progression of LVH.