Dataset Information

Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study.

ABSTRACT: BACKGROUND:Hypertension is a major modifiable risk factor for arteriosclerosis that can lead to target organ damage (TOD) of heart, kidneys, and peripheral arteries. A recent epigenome-wide association study for blood pressure (BP) identified 13 CpG sites, but it is not known whether DNA methylation at these sites is also associated with TOD. METHODS:In 1218 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a cohort of hypertensive sibships, we evaluated the associations between methylation at these 13 CpG sites measured in peripheral blood leukocytes and five TOD traits assessed approximately 5?years later. RESULTS:Ten significant associations were found after adjustment for age, sex, blood cell counts, time difference between CpG and TOD measurement, and 10 genetic principal components (FDR q?

SUBMITTER: Kho M

PROVIDER: S-EPMC7488710 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study.

Kho Minjung M Zhao Wei W Ratliff Scott M SM Ammous Farah F Mosley Thomas H TH Shang Lulu L Kardia Sharon L R SLR Zhou Xiang X Smith Jennifer A JA

BMC medical genomics 20200911 1

<h4>Background</h4>Hypertension is a major modifiable risk factor for arteriosclerosis that can lead to target organ damage (TOD) of heart, kidneys, and peripheral arteries. A recent epigenome-wide association study for blood pressure (BP) identified 13 CpG sites, but it is not known whether DNA methylation at these sites is also associated with TOD.<h4>Methods</h4>In 1218 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a cohort of hypertensive sibships, we ...[more]

PMID: 32917208

Similar Datasets

Project description:BackgroundDNA methylation, an epigenetic mechanism modulated by lifestyle and environmental factors, may be an important biomarker of complex diseases including cardiovascular diseases (CVD) and subclinical atherosclerosis.MethodsDNA methylation in peripheral blood samples from 391 African-Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) was assessed at baseline, and atherosclerosis was assessed 5 and 12 years later. Using linear mixed models, we examined the association between previously identified CpGs for coronary artery calcification (CAC) and carotid plaque, both individually and aggregated into methylation risk scores (MRSCAC and MRScarotid), and four measures of atherosclerosis (CAC, abdominal aorta calcification (AAC), ankle-brachial index (ABI), and multi-site atherosclerosis based on gender-specific quartiles of the single-site measures). We also examined the association between four epigenetic age acceleration measures (IEAA, EEAA, PhenoAge acceleration, and GrimAge acceleration) and the four atherosclerosis measures. Finally, we characterized the temporal stability of the epigenetic measures using repeated DNA methylation measured 5 years after baseline (N = 193).ResultsAfter adjusting for CVD risk factors, four CpGs (cg05575921(AHRR), cg09935388 (GFI1), cg21161138 (AHRR), and cg18168448 (LRRC52)) were associated with multi-site atherosclerosis (FDR < 0.1). cg05575921 was also associated with AAC and cg09935388 with ABI. MRSCAC was associated with ABI (Beta = 0.016, P = 0.006), and MRScarotid was associated with both AAC (Beta = 0.605, equivalent to approximately 1.8-fold increase in the Agatston score of AAC, P = 0.004) and multi-site atherosclerosis (Beta = 0.691, P = 0.002). A 5-year increase in GrimAge acceleration (~ 1 SD) was associated with a 1.6-fold (P = 0.012) increase in the Agatston score of AAC and 0.7 units (P = 0.0003) increase in multi-site atherosclerosis, all after adjusting for CVD risk factors. All epigenetic measures were relatively stable over 5 years, with the highest intraclass correlation coefficients observed for MRScarotid and GrimAge acceleration (0.87 and 0.89, respectively).ConclusionsWe found evidence of an association between DNA methylation and atherosclerosis at multiple vascular sites in a sample of African-Americans. Further evaluation of these potential biomarkers is warranted to deepen our understanding of the relationship between epigenetics and atherosclerosis.

Project description:BackgroundEpigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries.MethodsWe investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996-2000), and measures of target organ damage were assessed in a follow-up visit (2000-2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated.ResultsAfter adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p?=?0.004), relative wall thickness (RWT, p?=?0.022), and left ventricular mass index (LVMI, p?=?0.007), and with lower ankle-brachial index (ABI, p?=?0.014). EEAA was associated with higher LVMI (p?=?0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p?<?0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed.ConclusionsMeasures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.

Project description:<p><b>The Genetic Epidemiology Network of Arteriopathy (GENOA):</b> GENOA is one of four research networks that form the NHLBI Family Blood Pressure Program (FBPP). From its inception in 1995, GENOA's long-term objective was to elucidate the genetics of hypertension and its arteriosclerotic target-organ damage, including both atherosclerotic (macrovascular) and arteriolosclerotic (microvascular) complications involving the heart, brain, kidneys, and peripheral arteries. Two GENOA cohorts were originally ascertained (1995-2000) through sibships in which at least 2 siblings had essential hypertension diagnosed prior to age 60 years. All siblings in the sibship were invited to participate, both normotensive and hypertensive. These include non-Hispanic White Americans from Rochester, MN (n =1583 at the 1st exam) and African Americans from Jackson, MS (N=1854 at the 1st exam). During the second exam (2000-2005), approximately 80% of participants were re-recruited. The GENOA data consists of biological samples (DNA, serum, urine) as well as demographic, anthropometric, environmental, clinical, biochemical, physiological, and genetic data for understanding the genetic predictors of diseases of the heart, brain, kidney, and peripheral arteries.</p> <p><b>Family Blood Pressure Program (FBPP):</b> GENOA's parent program, the FBPP, is an unprecedented collaboration to identify genes influencing blood pressure (BP) levels, hypertension, and its target-organ damage. This program has conducted over 21,000 physical examinations, assembled a shared database of several hundred BP and hypertension-related phenotypic measurements, completed genome-wide linkage analyses for BP, hypertension, and hypertension associated risk factors and complications, and published over 130 manuscripts on program findings. The FBPP emerged from what was initially funded as four independent networks of investigators (HyperGEN, GenNet, SAPPHIRe and GENOA) competing to identify genetic determinants of hypertension in multiple ethnic groups. Realizing the greater likelihood of success through collaboration, the investigators began working together during the first funding cycle (1995-2000) and formalized this arrangement in the second cycle (2000-2005), creating a single confederation with program-wide and network-specific goals.</p>

Dataset Information

Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study.

Publications

Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets