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Genetic and Epigenetic Contributions to Hypertension and Blood Pressure Response...
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Genetic and Epigenetic Contributions to Hypertension and Blood Pressure Response to Interventions

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (30 May 2022) | Viewed by 8058

Special Issue Editor

Prof. Dr. Donna K. Arnett

E-Mail Website
Guest Editor
College of Public Health, University of Kentucky, Lexington, KY, USA
Interests: hypertension; cardiovascular disease; lipids; gene-environment interaction; pharmacogenomics; genome-wide association studies; epigenetics; metabolomics

Special Issue Information

Dear Colleagues,

 

Blood pressure is an established heritable trait, and numerous publications have reported genetic and epigenetic variants that are associated with the phenotype.  Relatives of hypertensive family members are at a two to four-fold risk of developing hypertension.  Monogenic forms of hypertension are well established.  While there has been tremendous success in understanding the monogenic forms of hypertension, there remains a large portion of genetic variation in blood pressure unexplained, and the genetic causes of “essential” hypertension remain elusive.  However, the newer -omic advancements have enabled more powerful research tools to discover the common and rare genetic variants associated with blood pressure, its related traits, and its response to interventions (e.g., a high salt diet or antihypertensive medication class), lending hope to furthering our understanding of the underlying genetic architecture of a disease that affects more than one billion individuals around the world.  The large genome-wide association studies of common variants have identified dozens of outstanding genetic candidate genes for hypertension, although they typically contribute a small amount to the overall heritability.  Whole genome sequencing offers an excellent opportunity to expand the search for more rare variants that may contribute to blood pressure.  The use of polygenic risk scores for hypertension are emerging.  These polygenic risk scores may be useful in the future to predict future hypertension, but perhaps could also be employed to predict the best class of treatment for hypertension that align with variants in the risk score.  Epigenetic approaches for hypertension and its related traits (e.g., renal, cardiovascular) have also recently elucidated potential new pathways for hypertension development, prevention, and possible treatment options.  The newer field of metabolomics also holds promise as a platform for discovery of the metabolic causes of hypertension and potential new biomarkers for early detection and prevention of future risk.   This special issue will explore a variety of these -omic approaches to understanding blood pressure, hypertension and its target organ consequences and blood pressure response to interventions.

Prof. Dr. Donna K. Arnett
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hypertension 
  • genomics 
  • epigenetics 
  • metabolomics 
  • pharmacogenetics 
  • blood pressure 
  • target organ damage

Published Papers (4 papers)

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Research

21 pages, 2302 KiB  
Article
The Interplay of Epigenetic, Genetic, and Traditional Risk Factors on Blood Pressure: Findings from the Health and Retirement Study
by Xinman Zhang, Farah Ammous, Lisha Lin, Scott M. Ratliff, Erin B. Ware, Jessica D. Faul, Wei Zhao, Sharon L. R. Kardia and Jennifer A. Smith
Genes 2022, 13(11), 1959; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13111959 - 27 Oct 2022
Viewed by 1751
Abstract
The epigenome likely interacts with traditional and genetic risk factors to influence blood pressure. We evaluated whether 13 previously reported DNA methylation sites (CpGs) are associated with systolic (SBP) or diastolic (DBP) blood pressure, both individually and aggregated into methylation risk scores (MRS), [...] Read more.
The epigenome likely interacts with traditional and genetic risk factors to influence blood pressure. We evaluated whether 13 previously reported DNA methylation sites (CpGs) are associated with systolic (SBP) or diastolic (DBP) blood pressure, both individually and aggregated into methylation risk scores (MRS), in 3070 participants (including 437 African ancestry (AA) and 2021 European ancestry (EA), mean age = 70.5 years) from the Health and Retirement Study. Nine CpGs were at least nominally associated with SBP and/or DBP after adjusting for traditional hypertension risk factors (p < 0.05). MRSSBP was positively associated with SBP in the full sample (β = 1.7 mmHg per 1 standard deviation in MRSSBP; p = 2.7 × 10−5) and in EA (β = 1.6; p = 0.001), and MRSDBP with DBP in the full sample (β = 1.1; p = 1.8 × 10−6), EA (β = 1.1; p = 7.2 × 10−5), and AA (β = 1.4; p = 0.03). The MRS and BP-genetic risk scores were independently associated with blood pressure in EA. The effects of both MRSs were weaker with increased age (pinteraction < 0.01), and the effect of MRSDBP was higher among individuals with at least some college education (pinteraction = 0.02). In AA, increasing MRSSBP was associated with higher SBP in females only (pinteraction = 0.01). Our work shows that MRS is a potential biomarker of blood pressure that may be modified by traditional hypertension risk factors. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Contributions to Hypertension and Blood Pressure Response to Interventions)
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13 pages, 1808 KiB  
Article
Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study
by Alana C. Jones, Amit Patki, Steven A. Claas, Hemant K. Tiwari, Ninad S. Chaudhary, Devin M. Absher, Leslie A. Lange, Ethan M. Lange, Wei Zhao, Scott M. Ratliff, Sharon L. R. Kardia, Jennifer A. Smith, Marguerite R. Irvin and Donna K. Arnett
Genes 2022, 13(10), 1700; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13101700 - 22 Sep 2022
Viewed by 1668
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Contributions to Hypertension and Blood Pressure Response to Interventions)
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17 pages, 1122 KiB  
Article
Life-Course Associations between Blood Pressure-Related Polygenic Risk Scores and Hypertension in the Bogalusa Heart Study
by Xiao Sun, Yang Pan, Ruiyuan Zhang, Ileana De Anda-Duran, Zhijie Huang, Changwei Li, Mengyao Shi, Alexander C. Razavi, Lydia A. Bazzano, Jiang He, Tamar Sofer and Tanika N. Kelly
Genes 2022, 13(8), 1473; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13081473 - 18 Aug 2022
Cited by 3 | Viewed by 1704
Abstract
Genetic information may help to identify individuals at increased risk for hypertension in early life, prior to the manifestation of elevated blood pressure (BP) values. We examined 369 Black and 832 White Bogalusa Heart Study (BHS) participants recruited in childhood and followed for [...] Read more.
Genetic information may help to identify individuals at increased risk for hypertension in early life, prior to the manifestation of elevated blood pressure (BP) values. We examined 369 Black and 832 White Bogalusa Heart Study (BHS) participants recruited in childhood and followed for approximately 37 years. The multi-ancestry genome-wide polygenic risk scores (PRSs) for systolic BP (SBP), diastolic BP (DBP), and hypertension were tested for an association with incident hypertension and stage 2 hypertension using Cox proportional hazards models. Race-stratified analyses were adjusted for baseline age, age2, sex, body mass index, genetic principal components, and BP. In Black participants, each standard deviation increase in SBP and DBP PRS conferred a 38% (p = 0.009) and 22% (p = 0.02) increased risk of hypertension and a 74% (p < 0.001) and 50% (p < 0.001) increased risk of stage 2 hypertension, respectively, while no association was observed with the hypertension PRSs. In Whites, each standard deviation increase in SBP, DBP, and hypertension PRS conferred a 24% (p < 0.05), 29% (p = 0.01), and 25% (p < 0.001) increased risk of hypertension, and a 27% (p = 0.08), 29% (0.01), and 42% (p < 0.001) increased risk of stage 2 hypertension, respectively. The addition of BP PRSs to the covariable-only models generally improved the C-statistics (p < 0.05). Multi-ancestry BP PRSs demonstrate the utility of genomic information in the early life prediction of hypertension. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Contributions to Hypertension and Blood Pressure Response to Interventions)
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14 pages, 897 KiB  
Article
Genetic Contributors of Efficacy and Adverse Metabolic Effects of Chlorthalidone in African Americans from the Genetics of Hypertension Associated Treatments (GenHAT) Study
by Nicole D. Armstrong, Vinodh Srinivasasainagendra, Lakshmi Manasa S. Chekka, Nam H. K. Nguyen, Noor A. Nahid, Alana C. Jones, Rikki M. Tanner, Bertha A. Hidalgo, Nita A. Limdi, Steven A. Claas, Yan Gong, Caitrin W. McDonough, Rhonda M. Cooper-DeHoff, Julie A. Johnson, Hemant K. Tiwari, Donna K. Arnett and Marguerite R. Irvin
Genes 2022, 13(7), 1260; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13071260 - 15 Jul 2022
Cited by 1 | Viewed by 2142
Abstract
Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies [...] Read more.
Hypertension is a leading risk factor for cardiovascular disease mortality. African Americans (AAs) have the highest prevalence of hypertension in the United States, and to alleviate the burden of hypertension in this population, better control of blood pressure (BP) is needed. Previous studies have shown considerable interpersonal differences in BP response to antihypertensive treatment, suggesting a genetic component. Utilizing data from 4297 AA participants randomized to chlorthalidone from the Genetics of Hypertension Associated Treatments (GenHAT) study, we aimed to identify variants associated with the efficacy of chlorthalidone. An additional aim was to find variants that contributed to changes in fasting glucose (FG) in these individuals. We performed genome-wide association analyses on the change of systolic and diastolic BP (SBP and DBP) over six months and FG levels over 24 months of treatment. We sought replication in the International Consortia of Pharmacogenomics Studies. We identified eight variants statistically associated with BP response and nine variants associated with FG response. One suggestive LINC02211-CDH9 intergenic variant was marginally replicated with the same direction of effect. Given the impact of hypertension in AAs, this study implies that understanding the genetic background for BP control and glucose changes during chlorthalidone treatment may help prevent adverse cardiovascular events in this population. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Contributions to Hypertension and Blood Pressure Response to Interventions)
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