scholarly journals Genome-wide analysis of DNA methylation and risk of cardiovascular disease in a Chinese population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan Gao ◽  
Huifang Pang ◽  
Bowang Chen ◽  
ChaoQun Wu ◽  
Yanping Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
High Risk ◽  
Area Under The Curve ◽  
Independent Set ◽  
Enrichment Analysis ◽  
Cardiac Risk ◽  
Genome Wide ◽  
Baseline Characteristics

Abstract Background Systemic studies of association of genome-wide DNA methylated sites with cardiovascular disease (CVD) in prospective cohorts are lacking. Our aim was to identify DNA methylation sites associated with the risk of CVD and further investigate their potential predictive value in CVD development for high-risk subjects. Methods We performed an epigenome-wide association study (EWAS) to identify CpGs related to CVD development in a Chinese population.We adopted a nested case–control design based on data from China PEACE Million Persons Project. A total of 83 cases who developed CVD events during follow-up and 83 controls who were matched with cases by age, sex, BMI, ethnicity, medications treatment and behavior risk factors were included in the discovery stage. Genome-wide DNA methylation from whole blood was detected using Infinium Human Methylation EPIC Beadchip (850 K). For significant CpGs [FDR(false discovery rate) < 0.005], we further validated in an independent cohort including 38 cases and 38 controls. Results In discovery set, we identified 8 significant CpGs (FDR < 0.005) associated with the risk of CVD after adjustment for cell components, demographic and cardiac risk factors and the first 5 principal components. Two of these identified CpGs (cg06901278 and cg09306458 in UACA) were replicated in another independent set (p < 0.05). Enrichment analysis in 787 individual genes from 1036 CpGs in discovery set revealed a significant enrichment for anatomical structure homeostasis as well as regulation of vesicle-mediated transport. Receiver operating characteristic (ROC) analysis showed that the model combined 8 CVD-related CpGs with baseline characteristics showed much better predictive effect for CVD occurrence compared with the model with baseline characteristics only [AUC (area under the curve) = 0.967, 95% CI (0.942 − 0.991); AUC = 0.621, 95% CI (0.536 − 0.706); p = 9.716E-15]. Conclusions Our study identified the novel CpGs associated with CVD development and revealed their additional predictive power in the risk of CVD for high-risk subjects.

Self-Reported Cardiac Risk Factors in Emergency Department Nurses and Paramedics

2000 ◽  
Vol 15 (2) ◽  
pp. 14-17 ◽  
Author(s):  
Tyler W. Barrett ◽  
Valerie C. Norton ◽  
Matthew Busam ◽  
Julie Boyd ◽  
David J. Maron ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Emergency Department ◽  
High Risk ◽  
Cardiac Disease ◽  
Cardiac Risk ◽  
Smoking History ◽  
Cardiac Risk Factors ◽  
History Of ◽  
Very High

AbstractStudy Objective:Our objective was to assess the prevalence of cardiac risk factors in a sample of urban paramedics and emergency department (ED) nurses.Methods:We asked 175 paramedics and ED nurses working at a busy, urban ED to complete a cardiovascular risk assessment. The survey asked subjects to report smoking history, diet, exercise habits, weight, stress levels, medication use, history of hypertension or cardiac disease, family history of cardiovascular disease (CVD), and cholesterol level (if known)Results:129 of 175 surveys were returned (74% return rate) by 85 paramedics and 44 nurses. The percentages of paramedics and nurses at high or very high risk for cardiac disease were 48% and 41%, respectively. Forty-one percent of female respondents and 46% of male respondents were at high or very high risk. Cigarette smoking was reported in 19% of the paramedics and 14% of the nurses. The percentages of paramedics and nurses who reported hypertension were 13% and 11%, respectively. High cholesterol was reported in 31% of paramedics and 16% of nurses.Conclusions:Forty-eight percent of paramedics and 41% of ED nurses at this center are at high or very high risk for cardiovascular disease, by self-report. Efforts should be made to better educate and intervene in this population of health-care providers in order to reduce their cardiac risk.

scholarly journals Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

2021 ◽  
Author(s):  
Eliana Portilla-Fernández ◽  
Shih-Jen Hwang ◽  
Rory Wilson ◽  
Jane Maddock ◽  
W. David Hill ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Association Studies ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness

AbstractCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

scholarly journals Gene set enrichment analysis for genome-wide DNA methylation data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jovana Maksimovic ◽  
Alicia Oshlack ◽  
Belinda Phipson
Keyword(s):  
Dna Methylation ◽  
Enrichment Analysis ◽  
R Package ◽  
Gene Set Enrichment Analysis ◽  
Methylation Array ◽  
Gene Set ◽  
Genome Wide ◽  
Genome Methylation ◽  
Unbiased Gene ◽  
Gene Set Testing

AbstractDNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human genome. Methylation array analysis has primarily focused on preprocessing, normalization, and identification of differentially methylated CpGs and regions. GOmeth and GOregion are new methods for performing unbiased gene set testing following differential methylation analysis. Benchmarking analyses demonstrate GOmeth outperforms other approaches, and GOregion is the first method for gene set testing of differentially methylated regions. Both methods are publicly available in the missMethyl Bioconductor R package.

scholarly journals Parathyroid gland disorders and cardiovascular disease

2021 ◽  
Vol 27 (1) ◽  
pp. 64-72
Author(s):  
Tatiana L. Karonova ◽  
Karina A. Pogosian ◽  
Liubov G. Yanevskaya ◽  
Olga D. Belyaeva ◽  
Elena N. Grineva
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Parathyroid Gland ◽  
Cardiac Risk ◽  
Improve Quality ◽  
Disease Pathogenesis ◽  
Pth Level

The review provides systematic information on the relation between pathology of parathyroid glands and cardiovascular disease (CVD). Recent studies have shown that actions of parathyroid hormone (PTH) and calcium affect the heart and vasculature through downstream actions of their receptors in the myocardium and endothelial cells, which lead to higher incidence of CVD among patients with parathyroid gland disorders (PGD). The mechanisms underlying this association also include insulin resistance and altered renin-angiotensinaldosterone axis among patients with primary hyperparathyroidism. However, low calcium and PTH level in hypoparathyroid patients are characterized by higher values of arterial stiffness, electrocardiogram abnormalities, vascular atherosclerosis and remodeling. These factors contribute to low quality of life among those patients. Knowledge of cardiovascular disease pathogenesis in patients with hyper- or hypoparathyroidism could help to improve quality of diagnostic and treatment and decrease the burden of cardiac risk factors. This review will be of interest to endocrinologists and cardiologists, and other specialists.

THU0003 ALTERED DNA METHYLATION AND DIFFERENTIAL EXPRESSION OF GENES INFLUENCING CARDIOVASCULAR RISK AND IMMUNITY IN CD4+ T CELLS FROM SUBJECTS WITH PSORIATIC ARTHRITIS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 214.1-214
Author(s):  
I. Arias de la Rosa ◽  
M. D. López Montilla ◽  
J. Rodríguez ◽  
E. Ballester ◽  
C. Torres-Granados ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
T Cells ◽  
Cardiovascular Risk ◽  
Research Support ◽  
Insulin Resistant ◽  
Genome Wide ◽  
Differentially Methylated Genes

Background:Cardiovascular risk factors are increased in Psoriatic Arthritis (PsA). In fact, around 60% out of PsA patients display insulin resistance (IR), a hallmark of metabolic syndrome, which might significantly contribute to the cardiovascular disease. Latest studies suggested that inflammatory and metabolic disorders may be under epigenetic control, including DNA methylation. DNA methylation is an unexplored area in the field of PsA.Objectives:To study the alterations in the genome-wide DNA methylation profile of CD4+T cells from PsA patients and its relationship with its pathology and the risk of cardiovascular comorbidity.Methods:Twenty healthy controls (HC) and 20 PsA patients were included in the study. PsA patients were classified into insulin resistant and non-insulin resistant according to HOMA-IR index. CD4+T lymphocytes were isolated from peripheral blood by positive immunomagnetic selection. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs (TSS1500, TSS200, 5UTR, 3UTR, first exon, gene body). Beta values (β) estimating methylation levels were obtained at each CpG site, and differentially methylated genes (DMG) between PsA and HC were identified. Functional classification of these genes was carried out through gene ontology analysis (PANTHER database). Gene expression analysis of the selected genes was also evaluated by RT-PCR. Vascular parameters including carotid intima-media thickness (cIMT) and endothelial function was analyzed by ecodoppler and periflux respectively.Results:The genome-wide methylation analysis identified 112 DMGs including 41 hypomethylated and 71 hypermethylated. These differentially methylated genes were enriched with several signaling pathways and disease categories including immune response, metabolic processes, oxidative stress, vascular and inflammatory pathways. The altered gene expression of selected genes with altered methylation levels in PsA was also validated. Correlation and association analysis of these DMGs with clinical and analytical variables, cardiovascular risk factors and endothelial microvascular function revealed that the degree of methylation of these genes was significantly associated with cIMT (IGF1R, NDRG3, SMYD3, HLA-DRB1, WDR70), arterial pressure (METT5D1, NRDG3, ADAM17, SMYD3, WNK1, CBX1), insulin resistance (AKAP13, SEMA6D, PLCB1), altered lipid profile and atherogenic index (MYBL1, METT5D1, MAN2A1, SLC1A7, SEMA6D, PLCB1, TLK1, SDK1, CBX1), inflammation (MYBL1, NDUFA5, METT5D1, SEMA6D, PLCB1, TLK1), and endothelial dysfunction (ADAMST10, GPCPD1, CCDC88A). In addition, this analysis also identified 435 DMGs including 280 hypomethylated and 155 hypermethylated in CD4+T cells from IR-PsA vs non IR-PsA patients. Between these two groups of PsA patients, CHUK, SERINC1, RUNX1, TTYH2, TXNDC11, FAF1, BICD1, SCD5, PDE5A, FAS, NFIA and GRP75 displayed the most significantly altered methylation, suggesting the role of these genes in the metabolic complications associated with PsA.Conclusion:These findings help our understanding of the pathogenesis of PsA and advance epigenetic studies in regards to this disease and the cardiometabolic comorbidities associated. Funded by ISCIII (PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER.Disclosure of Interests:Iván Arias de la Rosa: None declared, María Dolores López Montilla Speakers bureau: Celgene, Javier Rodríguez: None declared, Esteban Ballester: None declared, Carmen Torres-Granados: None declared, Carlos Perez-Sanchez: None declared, Maria del Carmen Abalos-Aguilera: None declared, Gómez García Ignacio: None declared, Desiree Ruiz: None declared, Alejandra M. Patiño-Trives: None declared, María Luque-Tévar: None declared, Eduardo Collantes-Estévez Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Alejandro Escudero Contreras Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene.

scholarly journals Genome-wide identification of DNA methylation QTLs in whole blood highlights pathways for cardiovascular disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Tianxiao Huan ◽  
Roby Joehanes ◽  
Ci Song ◽  
Fen Peng ◽  
Yichen Guo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Whole Blood ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Disease Associations ◽  
Independent Replication ◽  
Functional Mechanisms

Abstract Identifying methylation quantitative trait loci (meQTLs) and integrating them with disease-associated variants from genome-wide association studies (GWAS) may illuminate functional mechanisms underlying genetic variant-disease associations. Here, we perform GWAS of >415 thousand CpG methylation sites in whole blood from 4170 individuals and map 4.7 million cis- and 630 thousand trans-meQTL variants targeting >120 thousand CpGs. Independent replication is performed in 1347 participants from two studies. By linking cis-meQTL variants with GWAS results for cardiovascular disease (CVD) traits, we identify 92 putatively causal CpGs for CVD traits by Mendelian randomization analysis. Further integrating gene expression data reveals evidence of cis CpG-transcript pairs causally linked to CVD. In addition, we identify 22 trans-meQTL hotspots each targeting more than 30 CpGs and find that trans-meQTL hotspots appear to act in cis on expression of nearby transcriptional regulatory genes. Our findings provide a powerful meQTL resource and shed light on DNA methylation involvement in human diseases.

scholarly journals Epigenome-Wide DNA Methylation Analysis of Monozygotic Twins Discordant for Diurnal Preference

2015 ◽  
Vol 18 (6) ◽  
pp. 662-669 ◽  
Author(s):  
Chloe C. Y. Wong ◽  
Michael J. Parsons ◽  
Kathryn J. Lester ◽  
Joe Burrage ◽  
Thalia C. Eley ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Circadian Clock ◽  
Monozygotic Twins ◽  
Enrichment Analysis ◽  
Genome Wide ◽  
Analysis Strategy ◽  
Diurnal Preference ◽  
Significant Enrichment ◽  
Longitudinal Twin Study ◽  
Mz Twins

Diurnal preference is an individual's preference for daily activities and sleep timing and is strongly correlated with the underlying circadian clock and the sleep-wake cycle validating its use as an indirect circadian measure in humans. Recent research has implicated DNA methylation as a mechanism involved in the regulation of the circadian clock system in humans and other mammals. In order to evaluate the extent of epigenetic differences associated with diurnal preference, we examined genome-wide patterns of DNA methylation in DNA from monozygotic (MZ) twin-pairs discordant for diurnal preference. MZ twins were selected from a longitudinal twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. Fifteen pairs of MZ twins were identified in which one member scored considerably higher on the Horne–Ostberg Morningness–Eveningness Questionnaire (MEQ) than the other. Genome-wide DNA methylation patterns were assessed in twins’ buccal cell DNA using the Illumina Infinium HumanMethylation450 BeadChips. Quality control and data pre-processing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. Our data indicate that DNA methylation differences are detectable in MZ twins discordant for diurnal preference. Moreover, downstream gene ontology (GO) enrichment analysis on the top-ranked diurnal preference associated DMPs revealed significant enrichment of pathways that have been previously associated with circadian rhythm regulation, including cell adhesion processes and calcium ion binding.

scholarly journals The Use of Lee and Co-Workers’ Index to Assist a Risk Adjusted Audit of Perioperative Cardiac Outcome

2008 ◽  
Vol 36 (2) ◽  
pp. 167-173 ◽  
Author(s):  
P. J. Moran ◽  
T. Ghidella ◽  
G. Power ◽  
A. S. Jenkins ◽  
D. Whittle
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Positive Result ◽  
Cardiac Event ◽  
Risk Index ◽  
Cardiac Risk ◽  
Noncardiac Surgery ◽  
Frequent Use ◽  
Cardiac Outcome ◽  
The Impact

Lee and co-workers’ revised cardiac risk index was used to study the perioperative cardiac outcome of 296 patients. The index uses a history of ischaemic heart disease, congestive cardiac failure, diabetes treated with insulin, a creatinine greater than 180 μmol/l, cerebrovascular disease and high risk surgery as the risk factors involved in predicting a perioperative cardiac event. It was derived on the basis of data from patients over the age of 50 years undergoing elective, noncardiac surgery with an expected inpatient stay of two or more days. The presence of one, two and three or more risk factors predicted a risk of a major cardiac event of 1.3% (95% confidence interval [CI] 0.7 to 2.1), 3.6% (95% CI 2.1 to 5.6) and 9% (95% CI 5.5 to 13.8) respectively in Lee's derivation group of 2,893 patients. In our audit of 296 patients we observed a cardiac event rate of 0.8% (95% CI 0 to 2.3%), 6.7% (95% CI 1.6 to 10%) and 2% (95% CI 0 to 5.9%), in patients with one, two and three or more risk factors respectively. The more frequent use of ECGs and troponin levels in the routine postoperative care of high risk patients undergoing major noncardiac surgery is recommended on the basis of the frequency of a positive result and the impact of a positive result on a patient's management.

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