학술논문
Multi-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed MESA.
Document Type
Article
Author
Hu, Xiaowei; Logan, Jeongok G.; Kwon, Younghoon; Lima, Joao A. C.; Jacobs, David R.; Duprez, Daniel; Brumback, Lyndia; Taylor, Kent D.; Durda, Peter; Johnson, W. Craig; Cornell, Elaine; Guo, Xiuqing; Liu, Yongmei; Tracy, Russell P.; Blackwell, Thomas W.; Papanicolaou, George; Mitchell, Gary F.; Rich, Stephen S.; Rotter, Jerome I.; Van Den Berg, David J.
Source
Subject
*AORTA
*ARTERIAL diseases
*GENE expression
*DNA methylation
*INDIVIDUALIZED medicine
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Language
ISSN
2045-2322
Abstract
Despite the prognostic value of arterial stiffness (AS) and pulsatile hemodynamics (PH) for cardiovascular morbidity and mortality, epigenetic modifications that contribute to AS/PH remain unknown. To gain a better understanding of the link between epigenetics (DNA methylation) and AS/PH, we examined the relationship of eight measures of AS/PH with CpG sites and co-methylated regions using multi-ancestry participants from Trans-Omics for Precision Medicine (TOPMed) Multi-Ethnic Study of Atherosclerosis (MESA) with sample sizes ranging from 438 to 874. Epigenome-wide association analysis identified one genome-wide significant CpG (cg20711926-CYP1B1) associated with aortic augmentation index (AIx). Follow-up analyses, including gene set enrichment analysis, expression quantitative trait methylation analysis, and functional enrichment analysis on differentially methylated positions and regions, further prioritized three CpGs and their annotated genes (cg23800023-ETS1, cg08426368-TGFB3, and cg17350632-HLA-DPB1) for AIx. Among these, ETS1 and TGFB3 have been previously prioritized as candidate genes. Furthermore, both ETS1 and HLA-DPB1 have significant tissue correlations between Whole Blood and Aorta in GTEx, which suggests ETS1 and HLA-DPB1 could be potential biomarkers in understanding pathophysiology of AS/PH. Overall, our findings support the possible role of epigenetic regulation via DNA methylation of specific genes associated with AIx as well as identifying potential targets for regulation of AS/PH. [ABSTRACT FROM AUTHOR]