Is Any Cardiovascular Disease-Specific DNA Methylation Biomarker Within Reach?

2020 ◽  
Vol 22 (10) ◽  
Author(s):  
Carmen de la Rocha ◽  
Silvio Zaina ◽  
Gertrud Lund
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Disease Specific

15 LONGITUDINAL EVALUATION OF MUCOSAL DNA METHYLATION IN ULCERATIVE COLITIS SHOWS DISEASE-SPECIFIC CHANGES

2020 ◽  
Vol 158 (3) ◽  
pp. S50-S51
Author(s):  
Suresh Venkateswaran ◽  
Varun Kilaru ◽  
Hari Somineni ◽  
Jason Matthews ◽  
Jeffrey Hyams ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dna Methylation ◽  
Longitudinal Evaluation ◽  
Disease Specific

scholarly journals DNA methylation and gene expression integration in cardiovascular disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guillermo Palou-Márquez ◽  
Isaac Subirana ◽  
Lara Nonell ◽  
Alba Fernández-Sanlés ◽  
Roberto Elosua
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Diseases ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Risk Function ◽  
Predictive Biomarkers ◽  
Independent Study ◽  
Cell Type

Abstract Background The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. Results Four independent latent factors (9, 19, 21—only in women—and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. Conclusions Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

scholarly journals The epigenetic etiology of cardiovascular disease in a longitudinal Swedish twin study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xueying Qin ◽  
Ida K. Karlsson ◽  
Yunzhang Wang ◽  
Xia Li ◽  
Nancy Pedersen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cvd Risk ◽  
Significance Level ◽  
Latent Trajectory ◽  
Lagged Effects ◽  
The Cross ◽  
Level 2 ◽  
Cardiometabolic Traits

Abstract Background Studies on DNA methylation have the potential to discover mechanisms of cardiovascular disease (CVD) risk. However, the role of DNA methylation in CVD etiology remains unclear. Results We performed an epigenome-wide association study (EWAS) on CVD in a longitudinal sample of Swedish twins (535 individuals). We selected CpGs reaching the Bonferroni-corrected significance level (2 $$\times$$ ×  10–7) or the top-ranked 20 CpGs with the lowest P values if they did not reach this significance level in EWAS analysis associated with non-stroke CVD, overall stroke, and ischemic stroke, respectively. We further applied a bivariate autoregressive latent trajectory model with structured residuals (ALT-SR) to evaluate the cross-lagged effect between DNA methylation of these CpGs and cardiometabolic traits (blood lipids, blood pressure, and body mass index). Furthermore, mediation analysis was performed to evaluate whether the cross-lagged effects had causal impacts on CVD. In the EWAS models, none of the CpGs we selected reached the Bonferroni-corrected significance level. The ALT-SR model showed that DNA methylation levels were more likely to predict the subsequent level of cardiometabolic traits rather than the other way around (numbers of significant cross-lagged paths of methylation → trait/trait → methylation were 84/4, 45/6, 66/1 for the identified three CpG sets, respectively). Finally, we demonstrated significant indirect effects from DNA methylation on CVD mediated by cardiometabolic traits. Conclusions We present evidence for a directional association from DNA methylation on cardiometabolic traits and CVD, rather than the opposite, highlighting the role of epigenetics in CVD development.

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 Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaolian Gu ◽  
Linda Boldrup ◽  
Philip J. Coates ◽  
Robin Fahraeus ◽  
Elisabet Nylander ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Cpg Sites ◽  
Disease Specific

Differential DNA Methylation and Cardiometabolic Risk in African American Mother-Adolescent Dyads

2021 ◽  
pp. 109980042110390
Author(s):  
Amanda Elswick Gentry ◽  
Jo Robins ◽  
Mat Makowski ◽  
Wendy Kliewer
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
African American ◽  
African Americans ◽  
Waist Circumference ◽  
Low Income ◽  
Cardiometabolic Risk ◽  
Disease Risk ◽  
Cardiovascular Disease Risk

Background: Cardiovascular disease disproportionately affects African Americans as the leading cause of morbidity and mortality. Among African Americans, compared to other racial groups, cardiovascular disease onset occurs at an earlier age due to a higher prevalence of cardiometabolic risk factors, particularly obesity, hypertension and type 2 diabetes. Emerging evidence suggests that heritable epigenetic processes are related to increased cardiovascular disease risk, but this is largely unexplored in adolescents or across generations. Materials and Methods: In a cross-sectional descriptive pilot study in low-income African American mother-adolescent dyads, we examined associations between DNA methylation and the cardiometabolic indicators of body mass index, waist circumference, and insulin resistance. Results: Four adjacent cytosine and guanine nucleotides (CpG) sites were significantly differentially methylated and associated with C-reactive protein (CRP), 62 with waist circumference, and none to insulin resistance in models for both mothers and adolescents. Conclusion: Further study of the relations among psychological and environmental stressors, indicators of cardiovascular disease, risk, and epigenetic factors will improve understanding of cardiovascular disease risk so that preventive measures can be instituted earlier and more effectively. To our knowledge this work is the first to examine DNA methylation and cardiometabolic risk outcomes in mother-adolescent dyads.

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