Clinical Epigenetics最新文献

{"title":"DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain","authors":"Danni A. Gadd, Hannah M. Smith, Donncha Mullin, Ola Chybowska, Robert F. Hillary, Dorien M. Kimenai, Elena Bernabeu, Yipeng Cheng, Chloe Fawns-Ritchie, Archie Campbell, Danielle Page, Adele Taylor, Janie Corley, Maria Del C. Valdés-Hernández, Susana Muñoz Maniega, Mark E. Bastin, Joanna M. Wardlaw, Rosie M. Walker, Kathryn L. Evans, Andrew M. McIntosh, Caroline Hayward, Tom C. Russ, Sarah E. Harris, Paul Welsh, Naveed Sattar, Simon R. Cox, Daniel L. McCartney, Riccardo E. Marioni","doi":"10.1186/s13148-024-01734-7","DOIUrl":"https://doi.org/10.1186/s13148-024-01734-7","url":null,"abstract":"Plasma growth differentiation factor 15 (GDF15) and N‐terminal proB‐type natriuretic peptide (NT‐proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification. In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36–1.41, PFDR < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7–12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population. EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and validation of colorectal cancer tissue-specific methylation markers: a dual-center retrospective cohort study.","authors":"Qinxing Cao, Zhenjia Dan, Nengyi Hou, Li Yan, Xingmei Yuan, Hejiang Lu, Song Yu, Jiangping Zhang, Huasheng Xiao, Qiang Liu, Xiaoyong Zhang, Min Zhang, Minghui Pang","doi":"10.1186/s13148-024-01735-6","DOIUrl":"10.1186/s13148-024-01735-6","url":null,"abstract":"<p><strong>Background and purpose: </strong>Early detection, diagnosis, and treatment of colorectal cancer and its precancerous lesions can significantly improve patients' survival rates. The purpose of this research is to identify methylation markers specific to colorectal cancer tissues and validate their diagnostic capability in colorectal cancer and precancerous changes by measuring the level of DNA methylation in stool samples.</p><p><strong>Method: </strong>We analyzed samples from six cancer tissues and adjacent normal tissues and fecal samples from 758 participants, including 62 patients with interfering diseases. Bioinformatics databases were used to screen for candidate biomarkers for CRC, and quantitative methylation-specific PCR methods were applied for identification. The methylation levels of the candidate biomarkers in fecal and tissue samples were measured. Logistic regression and random forest models were built and validated using fecal sample data from one of the centers, and the independent or combined diagnostic value of the candidate biomarkers in fecal samples for CRC and precancerous lesions was analyzed. Finally, the diagnostic capability and stability of the model were validated at another medical center.</p><p><strong>Results: </strong>This study identified two colorectal cancer CpG sites with tissue specificity. These two biomarkers have certain diagnostic power when used individually, but their diagnostic value for colorectal cancer and colorectal adenoma is more significant when they are used in combination.</p><p><strong>Conclusion: </strong>The results indicate that a DNA methylation biomarker combined diagnostic model based on two CpG sites, cg13096260 and cg12587766, has the potential for screening and diagnosing precancerous lesions and colorectal cancer. Additionally, compared to traditional diagnostic models, machine learning algorithms perform better but may yield more false-positive results, necessitating further investigation.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitranscriptomics and epigenetics: two sides of the same coin?","authors":"Guglielmo Bove, Nunzio Del Gaudio, Lucia Altucci","doi":"10.1186/s13148-024-01729-4","DOIUrl":"https://doi.org/10.1186/s13148-024-01729-4","url":null,"abstract":"Gene expression is an intricate biological process that bridges gap between the genotype and the phenotype. Canonical and hereditable epigenetic mechanisms, such as histone and DNA modifications, regulate the release of genetic information encoded in DNA without altering the underlying sequence. Many other non-canonical players, such as chromatin regulators and noncoding RNAs, are also involved in regulating gene expression. Recently, RNA modifications (epitranscriptomics) have been shown to hold enormous potential in shaping cellular transcriptomes. However, their co-transcriptional nature and uncertain heritability mean that they fall outside the current definition of epigenetics, sparking an ongoing debate in the field. Here we will discuss the relationship between canonical and non-canonical epigenetic mechanisms that govern gene expression and offer our perspective on whether (or not) epitranscriptomic modifications can be classified as epigenetic mechanisms.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of tet methyl cytosine dioxygenase 3 (TET3) enhances cardiac fibrosis via modulating the DNA damage repair response.","authors":"Sandip Kumar Rath, Gunsmaa Nyamsuren, Björn Tampe, David Sung-Wen Yu, Melanie S Hulshoff, Denise Schlösser, Sabine Maamari, Michael Zeisberg, Elisabeth M Zeisberg","doi":"10.1186/s13148-024-01719-6","DOIUrl":"10.1186/s13148-024-01719-6","url":null,"abstract":"<p><strong>Background: </strong>Cardiac fibrosis is the hallmark of all forms of chronic heart disease. Activation and proliferation of cardiac fibroblasts are the prime mediators of cardiac fibrosis. Existing studies show that ROS and inflammatory cytokines produced during fibrosis not only signal proliferative stimuli but also contribute to DNA damage. Therefore, as a prerequisite to maintain sustained proliferation in fibroblasts, activation of distinct DNA repair mechanism is essential.</p><p><strong>Result: </strong>In this study, we report that TET3, a DNA demethylating enzyme, which has been shown to be reduced in cardiac fibrosis and to exert antifibrotic effects does so not only through its demethylating activity but also through maintaining genomic integrity by facilitating error-free homologous recombination (HR) repair of DNA damage. Using both in vitro and in vivo models of cardiac fibrosis as well as data from human heart tissue, we demonstrate that the loss of TET3 in cardiac fibroblasts leads to spontaneous DNA damage and in the presence of TGF-β to a shift from HR to the fast but more error-prone non-homologous end joining repair pathway. This shift contributes to increased fibroblast proliferation in a fibrotic environment. In vitro experiments showed TET3's recruitment to H2O2-induced DNA double-strand breaks (DSBs) in mouse cardiac fibroblasts, promoting HR repair. Overexpressing TET3 counteracted TGF-β-induced fibroblast proliferation and restored HR repair efficiency. Extending these findings to human cardiac fibrosis, we confirmed TET3 expression loss in fibrotic hearts and identified a negative correlation between TET3 levels, fibrosis markers, and DNA repair pathway alteration.</p><p><strong>Conclusion: </strong>Collectively, our findings demonstrate TET3's pivotal role in modulating DDR and fibroblast proliferation in cardiac fibrosis and further highlight TET3 as a potential therapeutic target.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization analysis reveals the combined effects of epigenetics and telomere biology in hematologic cancers.","authors":"Xin Zhuang, Peng Chen, Rong Yang, Xiaoying Man, Ruochen Wang, Yifen Shi","doi":"10.1186/s13148-024-01728-5","DOIUrl":"10.1186/s13148-024-01728-5","url":null,"abstract":"<p><strong>Background: </strong>Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks.</p><p><strong>Methods: </strong>This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR).</p><p><strong>Results: </strong>Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P < 0.05) and establish a causal relationship between telomere length and red blood cell indices such as RBC (OR = 1.121, P_IVW = 0.034), MCH (OR = 0.801, P_IVW = 2.046e-06), MCV (OR = 0.801, P_IVW = 0.001), and MCHC (OR = 0.813, P_IVW = 0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR = 1.026, P_IVW = 0.007).</p><p><strong>Conclusion: </strong>The study clarifies the relationships between telomere length, EAA, and hematological malignancies, further emphasizing the prognostic significance of telomere length and EAA. This deepens our understanding of the pathogenesis of hematological diseases, which can inform risk assessment and therapeutic strategies.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential white blood cell count and epigenetic clocks: a bidirectional Mendelian randomization study.","authors":"Manli Sun, Huan Yang, Yang Hu, Jiaqi Fan, Mingjing Duan, Jingqi Ruan, Shichang Li, Yang Xu, Yue Han","doi":"10.1186/s13148-024-01717-8","DOIUrl":"10.1186/s13148-024-01717-8","url":null,"abstract":"<p><strong>Background: </strong>Human aging and white blood cell (WBC) count are complex traits influenced by multiple genetic factors. Predictors of chronological age have been developed using epigenetic clocks. However, the bidirectional causal effects between epigenetic clocks and WBC count have not been fully examined.</p><p><strong>Methods: </strong>This study employed Mendelian randomization (MR) to analyze summary statistics from four epigenetic clocks involving 34,710 participants, alongside data from the Blood Cell Consortium encompassing 563,946 individuals. We primarily explored bidirectional causal relationships using the random-effects inverse-variance weighted method, supplemented by additional MR methods for comprehensive analysis. Additionally, multivariate MR was applied to investigate independent effects of WBC count on epigenetic age acceleration.</p><p><strong>Results: </strong>In the two-sample univariate MR (UVMR) analysis, we observed that a decrease in lymphocyte count markedly accelerated aging according to the PhenoAge, GrimAge, and HannumAge metrics (all P < 0.01, β < 0), though it did not affect Intrinsic Epigenetic Age Acceleration (IEAA). Conversely, an increase in neutrophil count significantly elevated PhenoAge levels (β: 0.38; 95% CI 0.14, 0.61; P = 1.65E-03 < 0.01). Reverse MR revealed no significant causal impacts of epigenetic clocks on overall WBC counts. Furthermore, in multivariate MR, the impact of lymphocyte counts on epigenetic aging metrics remained statistically significant. We also identified a marked causal association between neutrophil counts and PhenoAge, GrimAge, and HannumAge, with respective results showing strong associations (PhenoAge β: 0.78; 95% CI 0.47, 1.09; P = 8.26E-07; GrimAge β: 0.55; 95% CI 0.31, 0.79; P = 5.50E-06; HannumAge β: 0.42; 95% CI 0.18, 0.67; P = 6.30E-04). Likewise, eosinophil cell count demonstrated significant association with HannumAge (β: 0.33; 95% CI 0.13, 0.53; P = 1.43E-03 < 0.01).</p><p><strong>Conclusion: </strong>These findings demonstrated that within WBCs, lymphocyte and neutrophil counts exert irreversible and independent causal effects on the acceleration of PhenoAge, GrimAge, and HannumAge. Our findings highlight the critical role of WBCs in influencing epigenetic clocks and underscore the importance of considering immune parameters when interpreting epigenetic age.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics association study of DNA methylation and gene expression levels and diagnoses of cardiovascular diseases in Danish Twins.","authors":"Asmus Cosmos Skovgaard, Afsaneh Mohammadnejad, Hans Christian Beck, Qihua Tan, Mette Soerensen","doi":"10.1186/s13148-024-01727-6","DOIUrl":"10.1186/s13148-024-01727-6","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases (CVDs) are major causes of mortality and morbidity worldwide; yet the understanding of their molecular basis is incomplete. Multi-omics studies have significant potential to uncover these mechanisms, but such studies are challenged by genetic and environmental confounding-a problem that can be effectively reduced by investigating intrapair differences in twins. Here, we linked data on all diagnoses of the circulatory system from the nationwide Danish Patient Registry (spanning 1977-2022) to a study population of 835 twins holding genome-wide DNA methylation and gene expression data. CVD diagnoses were divided into prevalent or incident cases (i.e., occurring before or after blood sample collection (2007-2011)). The diagnoses were classified into four groups: cerebrovascular diseases, coronary artery disease (CAD), arterial and other cardiovascular diseases (AOCDs), and diseases of the veins and lymphatic system. Statistical analyses were performed by linear (prevalent cases) or cox (incident cases) regression analyses at both the individual-level and twin pair-level. Significant genes (p < 0.05) in both types of biological data and at both levels were inspected by bioinformatic analyses, including gene set enrichment analysis and interaction network analysis.</p><p><strong>Results: </strong>In general, more genes were found for prevalent than for incident cases, and bioinformatic analyses primarily found pathways of the immune system, signal transduction and diseases for prevalent cases, and pathways of cell-cell communication, metabolisms of proteins and RNA, gene expression, and chromatin organization groups for incident cases. This potentially reflects biology related to response to CVD (prevalent cases) and mechanisms related to regulation and development of disease (incident cases). Of specific genes, Myosin 1E was found to be central for CAD, and DEAD-Box Helicase 5 for AOCD. These genes were observed in both the prevalent and the incident analyses, potentially reflecting that their DNA methylation and gene transcription levels change both because of disease (prevalent cases) and prior disease (incident cases).</p><p><strong>Conclusion: </strong>We present novel biomarkers for CVD by performing multi-omics analysis in twins, hereby lowering the confounding due to shared genetics and early life environment-a study design that is surprisingly rare in the field of CVD, and where additional studies are highly needed.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological aging mediates the association between periodontitis and cardiovascular disease: results from a national population study and Mendelian randomization analysis.","authors":"Zhaoqi Zhang, Xingru Zhao, Shang Gao, An Li, Ke Deng, Kai Yang, Wei Liu, Mi Du","doi":"10.1186/s13148-024-01732-9","DOIUrl":"10.1186/s13148-024-01732-9","url":null,"abstract":"<p><strong>Background: </strong>The relationship between periodontitis and cardiovascular disease (CVD) has been extensively studied, but the role of biological aging in this relationship remains poorly understood. This study is dedicated to investigating the effect of periodontitis on the incidence of CVD and to elucidating the potential mediating role of biological aging. Furthermore, this study will seek to elucidate the causal association between periodontitis, CVD, and biological aging.</p><p><strong>Methods: </strong>We included 3269 participants from the National Health and Nutrition Examination Survey (2009-2014) with diagnostic information on periodontitis and composite CVD events. Biological aging was evaluated by utilizing both the Klemera-Doubal method's calculated biological age (KDMAge) and phenotypic age (PhenoAge). Logistic regression, restricted cubic spline (RCS) analysis, and subgroup analysis were used for data analysis. Mediation analysis was employed to explore the mediating role of biological aging. Subsequently, Mendelian randomization (MR) analyses were performed using genome-wide association study databases to explore potential causal relationships between periodontitis, CVD, and biological aging.</p><p><strong>Results: </strong>Periodontitis was associated with a higher risk of CVD. Participants with periodontitis were found to have increased levels of biological aging, and elevated levels of biological aging were associated with increased CVD risk. Mediation analyses showed a partial mediating effect of biological aging (PhenoAge: 44.6%; KDMAge: 22.9%) between periodontitis and CVD risk. MR analysis showed that periodontitis played a causal role in increasing the risk of small vessel stroke, while myocardial infarction was found to increase the risk of periodontitis. In addition, reverse MR analysis showed that phenotypic aging can increase the risk of periodontitis, and there is a two-way causal relationship between CVD and biological aging.</p><p><strong>Conclusions: </strong>Periodontitis is associated with an increased CVD risk, partially mediated by biological aging, with a complex causal interrelationship. Targeted interventions for periodontal health may slow the biological aging processes and reduce CVD risk.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation in cardiovascular disease and heart failure: novel prediction models?","authors":"Antonella Desiderio, Monica Pastorino, Michele Campitelli, Michele Longo, Claudia Miele, Raffaele Napoli, Francesco Beguinot, Gregory Alexander Raciti","doi":"10.1186/s13148-024-01722-x","DOIUrl":"10.1186/s13148-024-01722-x","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases (CVD) affect over half a billion people worldwide and are the leading cause of global deaths. In particular, due to population aging and worldwide spreading of risk factors, the prevalence of heart failure (HF) is also increasing. HF accounts for approximately 36% of all CVD-related deaths and stands as the foremost cause of hospitalization. Patients affected by CVD or HF experience a substantial decrease in health-related quality of life compared to healthy subjects or affected by other diffused chronic diseases.</p><p><strong>Main body: </strong>For both CVD and HF, prediction models have been developed, which utilize patient data, routine laboratory and further diagnostic tests. While some of these scores are currently used in clinical practice, there still is a need for innovative approaches to optimize CVD and HF prediction and to reduce the impact of these conditions on the global population. Epigenetic biomarkers, particularly DNA methylation (DNAm) changes, offer valuable insight for predicting risk, disease diagnosis and prognosis, and for monitoring treatment. The present work reviews current information relating DNAm, CVD and HF and discusses the use of DNAm in improving clinical risk prediction of CVD and HF as well as that of DNAm age as a proxy for cardiac aging.</p><p><strong>Conclusion: </strong>DNAm biomarkers offer a valuable contribution to improving the accuracy of CV risk models. Many CpG sites have been adopted to develop specific prediction scores for CVD and HF with similar or enhanced performance on the top of existing risk measures. In the near future, integrating data from DNA methylome and other sources and advancements in new machine learning algorithms will help develop more precise and personalized risk prediction methods for CVD and HF.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The response to influenza vaccination is associated with DNA methylation-driven regulation of T cell innate antiviral pathways.","authors":"Hongxiang Fu, Harry Pickering, Liudmilla Rubbi, Ted M Ross, Wanding Zhou, Elaine F Reed, Matteo Pellegrini","doi":"10.1186/s13148-024-01730-x","DOIUrl":"10.1186/s13148-024-01730-x","url":null,"abstract":"<p><strong>Background: </strong>The effect of vaccination on the epigenome remains poorly characterized. In previous research, we identified an association between seroprotection against influenza and DNA methylation at sites associated with the RIG-1 signaling pathway, which recognizes viral double-stranded RNA and leads to a type I interferon response. However, these studies did not fully account for confounding factors including age, gender, and BMI, along with changes in cell-type composition.</p><p><strong>Results: </strong>Here, we studied the influenza vaccine response in a longitudinal cohort vaccinated over two consecutive years (2019-2020 and 2020-2021), using peripheral blood mononuclear cells and a targeted DNA methylation approach. To address the effects of multiple factors on the epigenome, we designed a multivariate multiple regression model that included seroprotection levels as quantified by the hemagglutination-inhibition (HAI) assay test.</p><p><strong>Conclusions: </strong>Our findings indicate that 179 methylation sites can be combined as potential signatures to predict seroprotection. These sites were not only enriched for genes involved in the regulation of the RIG-I signaling pathway, as found previously, but also enriched for other genes associated with innate immunity to viruses and the transcription factor binding sites of BRD4, which is known to impact T cell memory. We propose a model to suggest that the RIG-I pathway and BRD4 could potentially be modulated to improve immunization strategies.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}