Multi-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed MESA
Year: 2023
Type: article
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.
Source: Scientific Reports
Authors: Xiaowei Hu, Jeongok G. Logan, Younghoon Kwon, Joao A. C. Lima, David R. Jacobs, Daniel Duprez, Lyndia Brumback, Kent D. Taylor, Peter Durda, W. Craig Johnson, Elaine Cornell, Xiuqing Guo, Yongmei Liu, Russell P. Tracy, Thomas W. Blackwell, George Papanicolaou, Gary F. Mitchell, Stephen S. Rich, Jerome I. Rotter, David J. Van Den Berg, Julio A. Chirinos, Timothy M. Hughes, Francine E. Garrett-Bakelman, Ani Manichaikul
Institutions: University of Virginia, University of Washington, Johns Hopkins University, University of Minnesota, The Lundquist Institute, Harbor–UCLA Medical Center, University of Vermont, Duke University, University of Michigan, National Heart, Lung, and Blood Institute, University of Southern California, University of Pennsylvania, Wake Forest University Health Sciences, Wake Forest University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,390
Awards: HeartShare: Next-Generation Phenomics to Define Heart Failure Subtypes and Treatment Targets - Clinical Centers, MESA, G1368206780, G1409423729, G1539384734, G1686417863, G1803853571, Wake Forest Clinical and Translational Science Award, Large Scale Sequencing and Analysis of Genomes, Blockade of calcium channels and beta adrenergic receptors for physiologic abnormalities in heart failure with preserved ejection fraction (BLOCK HFpEF), Rare variants and NHLBI traits in deeply phenotyped cohorts, G2225919419, G2262782284, G232264632, MESA, VASCULAR EFFECTS OF DIETARY SALT IN HUMANS WITH SALT-RESISTANT BP, Efficacy of Fenofibrate for COVID-19: A phase II randomized controlled trial, G2580996367, MESA, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G3570589137, G3647016462, G3687594596, MESA, G399481048, TITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), G4512137732, G4563812999, OPTION 3. 4/1/2014 - 3/31/2015. MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - READING CENTER, NHLBI, MESA, G5088122703, G5108002584, G514410172, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G5787256936, CHARGE consortium: omics discovery for CVD and aging phenotypes, G6095866717, G6359107525, G640430542, Institute for Clinical and Translational Research, MESA, G6514094751, MESA, Integrative genomic, transcriptomic and proteomic studies of pulmonary function and COPD, Clinical and Translational Science Award, Studies of Rare Genetic Variation in the Isolated Population of Sardinia, G8761005068, Developing Oral LT3 Therapy for Heart Failure, G9000019884, Subclinical Vascular Contributions to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis (MESA) Multisite Study of AD (Renewal), Targeting Skeletal Muscle Perfusion and Oxidative Capacity in HFpEF, Genetic determinants of thoracic aortic stiffness and remodeling, Cardiovascular Risk, Vascular and Kidney Damage in COVID-19 Survivors, Diabetes Research Center (DRC), Cardiovascular Consequences of Duchenne and Becker Muscular Dystrophinopathies, UCLA Clinical and Translational Science Institute
OpenAlex ID: W4387723079