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. 2022 Sep 22;13(10):1700.
doi: 10.3390/genes13101700.

Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study

Alana C Jones  1 , Amit Patki  2 , Steven A Claas  3 , Hemant K Tiwari  2 , Ninad S Chaudhary  1   4 , Devin M Absher  5 , Leslie A Lange  6   7 , Ethan M Lange  7   8 , Wei Zhao  9 , Scott M Ratliff  9 , Sharon L R Kardia  9 , Jennifer A Smith  9 , Marguerite R Irvin  1 , Donna K Arnett  3
Affiliations

Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study

Alana C Jones et al. Genes (Basel). .

Abstract

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular disease, and African Americans experience a disparate high risk of LVH. Genetic studies have identified potential candidate genes and variants related to the condition. Epigenetic modifications may continue to help unravel disease mechanisms. We used methylation and echocardiography data from 636 African Americans selected from the Hypertension Genetic Epidemiology Network (HyperGEN) to identify differentially methylated regions (DMRs) associated with LVH. DNA extracted from whole blood was assayed on Illumina Methyl450 arrays. We fit linear mixed models to examine associations between co-methylated regions and LV traits, and we then conducted single CpG analyses within significant DMRs. We identified associations between DMRs and ejection fraction (XKR6), LV internal diastolic dimension (TRAK1), LV mass index (GSE1, RPS15 A, PSMD7), and relative wall thickness (DNHD1). In single CpG analysis, CpG sites annotated to TRAK1 and DNHD1 were significant. These CpGs were not associated with LV traits in replication cohorts but the direction of effect for DNHD1 was consistent across cohorts. Of note, DNHD1, GSE1, and PSMD7 may contribute to cardiac structural function. Future studies should evaluate relationships between regional DNA methylation patterns and the development of LVH.

Keywords: DMR; DNA methylation; EWAS; epigenetics; left ventricular hypertrophy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biological features near (a) DNHD1, (b) GSE1, and (c) PSMD7 from ENCODE. Highlighted fragments correspond to the DMR position.
Figure 1
Figure 1
Biological features near (a) DNHD1, (b) GSE1, and (c) PSMD7 from ENCODE. Highlighted fragments correspond to the DMR position.
Figure 2
Figure 2
Manhattan & QQ Plot for RWT in HyperGEN. CpG sites in the DNHD1 DMR are highlighted in green. Lambda with genomic control for QQ plot = 0.998.
See this image and copyright information in PMC

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