Clinical Epigenetics最新文献

{"title":"Thirteen cases support the clinical significance of imprinting center 1 (IC1) microdeletions in Beckwith-Wiedemann syndrome.","authors":"Qiliang Ding, Zinandre Stander, Brandon J Elizalde, Erica S Stelmach, Jaime C Duncan, Noemi Vidal-Folch, Linda Hasadsri, Kandelaria M Rumilla, Wei Shen","doi":"10.1186/s13148-025-01873-5","DOIUrl":"https://doi.org/10.1186/s13148-025-01873-5","url":null,"abstract":"<p><p>Most Beckwith-Wiedemann syndrome (BWS) cases are sporadic; nonetheless, imprinting center 1 (IC1) microdeletions have been suggested as a rare cause of familial BWS, with ~ 20 reported cases. We report 13 cases from nine families with IC1 microdeletions. Recurrent 1.4-kb, 1.8-kb, and 2.2-kb deletions were observed. IC1 hypermethylation was identified in all families, and we established a statistically significant relationship between IC1 microdeletions and hypermethylation (OR: 108.17, p = 2.76e-13). This study confirms IC1 microdeletions as a cause of familial BWS, expands the understanding of their molecular mechanisms, and supports a Likely Pathogenic clinical classification for IC1 microdeletions.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"67"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975335","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":"Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature.","authors":"Quentin Sabbagh, Nathalie Ruiz-Pallares, Cassandra Rastin, Jacques Puechberty, Thomas Guignard, Claire Jeandel, Fanny Merklen, Pascal Pujol, Jennifer Kerkhof, Bekim Sadikovic, Mouna Barat-Houari, David Geneviève","doi":"10.1186/s13148-025-01879-z","DOIUrl":"https://doi.org/10.1186/s13148-025-01879-z","url":null,"abstract":"<p><p>Kabuki syndrome type 1 (KS1) is a monogenic disorder arising from pathogenic variants within KMT2D and characterized by syndromic neurodevelopmental delay. We report the retrospective identification of a causative AluY insertion within KMT2D in a genetically unsolved individual with typical KS1 features, after identification of a DNA methylation signature. This is the first documentation of Alu insertion as a molecular mechanism responsible for KS1. This study emphasizes the need for reanalyzing inconclusive sequencing data in individuals with gene-specific phenotypes and reinforces episignature as a reliable diagnostic tool when NGS approaches fail to provide conclusive results in individuals with rare diseases.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"69"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990042","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":"Associations between five indicators of epigenetic age acceleration and all-cause and cause-specific mortality among US adults aged 50 years and older.","authors":"Yun Zou, Jing Huang, Xiaoli Tang, Jixiong Xu","doi":"10.1186/s13148-025-01872-6","DOIUrl":"https://doi.org/10.1186/s13148-025-01872-6","url":null,"abstract":"<p><strong>Background: </strong>Although DNA methylation age estimators (DNAmAges) are reliable tools for predicting aging, their effectiveness in predicting mortality risk has not been fully validated. This study compared the predictive utility of five different DNAmAges (HorvathAge, HannumAge, PhenoAgeAge, GrimAge and GrimAge2) for all-cause and cause-specific mortality among adults aged ≥ 50 years.</p><p><strong>Methods: </strong>We screened 1966 participants adults aged ≥ 50 from the National Health and Nutrition Examination Survey (1999-2002) and linked them to the National Death Index to obtain cause and status of death. We used weighted Cox proportional hazards models to examine the associations between epigenetic age acceleration (EAA) measured by different DNAmAges and all-cause and cause-specific mortality in the general population, adjusting for various covariates including age, smoking status and chronic diseases. We used restricted cubic splines to explore nonlinear associations. Finally, stratified analyses were performed to assess the relationship between DNA age estimators and stratification variables.</p><p><strong>Results: </strong>The multivariable adjustment model showed that EAA measured by HorvathAge (AAHorvathAge), HannumAge (AAHannumAge), PhenoAge (AAPhenoAge), GrimAge (AAGrimAge) and GrimAge2 (AAGrimAge) were significantly associated with the risk of death, among which AAGrimAge and AAGrimAge2 had stronger statistical correlation and the correlation pattern was positively correlated. Specifically, each 5-year increase in AAGrimAge was associated with a 44% increased risk of all-cause death, a 33% increased risk of cardiovascular death and a 54% increased risk of non-cardiovascular death. And each 5-year increase in AAGrimAge2 was associated with a 40% increased risk of all-cause death, a 33% increased risk of cardiovascular death and a 47% increased risk of non-cardiovascular death. In contrast, AAHorvathAge, AAHannumAge and AAPhenoAge showed a J-shaped correlation with the risk of all-cause mortality and non-cardiovascular mortality, with the inflection points of all-cause mortality and non-cardiovascular mortality occurring at AAHorvathAge of 2.29 and 2.8, AAHannumAge of 3.07 and 2.97, and AAPhenoAge of - 7.65 and 7.04, respectively. No interaction was found between DNAmAges and stratification variables.</p><p><strong>Conclusions: </strong>AAGrimAge and AAGrimAge2 outperformed AAHorvathAge, AAHannumAge and AAPhenoAge in predicting mortality risk, and the association pattern was positive.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"66"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983727","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":"Regulation of nc886 (vtRNA2-1) RNAs is associated with cardiometabolic risk factors and diseases.","authors":"Sonja Rajić, Thomas Delerue, Justiina Ronkainen, Ruiyuan Zhang, Joanna Ciantar, Daria Kostiniuk, Pashupati P Mishra, Leo-Pekka Lyytikäinen, Nina Mononen, Laura Kananen, Annette Peters, Juliane Winkelmann, Marcus E Kleber, Stefan Lorkowski, Mika Kähönen, Terho Lehtimäki, Olli Raitakari, Melanie Waldenberger, Christian Gieger, Winfried März, Emily W Harville, Sylvain Sebert, Saara Marttila, Emma Raitoharju","doi":"10.1186/s13148-025-01871-7","DOIUrl":"https://doi.org/10.1186/s13148-025-01871-7","url":null,"abstract":"<p><p>Non-coding 886 (nc886, vtRNA2-1) is a polymorphically imprinted gene. The methylation status of this locus has been shown to be associated with periconceptional conditions, and both the methylation status and the levels of nc886 RNAs have been shown to associate with later-life health traits. We have previously shown that nc886 RNA levels are associated not only with the methylation status of the locus, but also with a genetic polymorphism upstream from the locus. In this study, we describe the genetic and epigenetic regulators that predict lifelong nc886 RNA levels, as well as their association with cardiometabolic disease (CMD) risk factors and events. We utilised six population cohorts and one CMD cohort comprising 9058 individuals in total. The association of nc886 RNA levels, as predicted by epigenetic and genetic regulators, with CMD phenotypes was analysed using regression models, with a meta-analysis of the results. The meta-analysis showed that individuals with upregulated nc886 RNA levels have higher diastolic blood pressure (β = 0.07, p = 0.008), lower HDL levels (β =  - 0.07, p = 0.006) and an increased incidence of type 2 diabetes (OR = 1.260, p = 0.013). Moreover, CMD patients with upregulated nc886 RNA levels have an increased incidence of stroke (OR = 1.581, p = 0.006) and death (OR = 1.290, p = 0.046). In conclusion, we show that individuals who are predicted to present elevated nc886 RNA levels have poorer cardiovascular health and are at an elevated risk of complications in secondary prevention. This unique mechanism yields metabolic variation in human populations, constituting a CMD risk factor that cannot be modified through lifestyle choices.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"68"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978992","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":"Integrative DNA methylome and transcriptome analysis identify potential genes on the influence of dilated cardiomyopathy-associated heart failure.","authors":"Zhenglong Guo, Yunfei Liu, Zhiming Zhou, Jianchao Chen, Lin Guo, Keke Liang, Yibin Hao, Bingtao Hao, Bin Yang, Shixiu Liao","doi":"10.1186/s13148-025-01876-2","DOIUrl":"https://doi.org/10.1186/s13148-025-01876-2","url":null,"abstract":"<p><strong>Objective: </strong>Dilated cardiomyopathy (DCM)-associated heart failure (HF) presents a significant clinical challenge, underlying epigenetic mechanisms remaining poorly understood. This study aims to investigate the interplay between DNA methylation and gene expression in the hearts of patients with DCM-associated HF (DCM-HF).</p><p><strong>Methods: </strong>Atrial tissues were collected from five healthy donors and five heart transplant recipients suffering from heart failure due to DCM. We conducted RNA-sequencing (RNA-seq) to analyze mRNA expression profiles and performed whole-genome bisulfite sequencing (WGBS) to evaluate DNA methylation levels. Correlation analyses between RNA-seq and WGBS data were executed by integrating differentially expressed genes (DEGs) with genes associated with differentially methylated regions (DMRs) located in the promoter regions.</p><p><strong>Results: </strong>The RNA-seq analysis identified a total of 681 DEGs, comprising 406 significantly downregulated genes and 275 upregulated genes in DCM-HF tissues, which were enriched in pathways related to cardiomyopathy. WGBS revealed 16,158 hypomethylated and 6,857 hypermethylated differentially methylated regions (DMRs), with 3,185 of these located in promoter regions. The integration of promoter-hypomethylated and hypermethylated DMRs-related genes (DMGs) with DEGs resulted in the identification of 46 hub genes associated with cardiac development and function. Protein-protein interaction and disease association analyses highlighted five key genes-NPPA, NPPB, ACTN2, NEBL, and MYO18B-that exhibited promoter hypomethylation and increased expression, potentially linked to the activity of transcription factors such as HIF1A and KLF4.</p><p><strong>Conclusions: </strong>These findings suggest that the epigenetic dysregulation of cardiac stress-response and structural genes contributes to the pathogenesis of DCM-HF. Furthermore, the detection of promoter methylation levels in these loci may offer new opportunities for developing diagnostic tools and therapeutic strategies for DCM-HF management.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"64"},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961547","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 associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins.","authors":"Jingxian Li, Jia Luo, Tong Wang, Xiaocao Tian, Chunsheng Xu, Weijing Wang, Dongfeng Zhang","doi":"10.1186/s13148-025-01869-1","DOIUrl":"https://doi.org/10.1186/s13148-025-01869-1","url":null,"abstract":"<p><strong>Background: </strong>To identify nongenetic factors influences on DNA methylation (DNAm) variations associated with blood Alanine Aminotransferase (ALT) concentration, this study conducted an epigenome-wide association study (EWAS) on Chinese monozygotic twins.</p><p><strong>Methods: </strong>A total of 61 pairs of Chinese monozygotic twins involved in this study. Whole blood samples were analyzed for DNAm profiling using the Reduced Representation Bisulfite Sequencing (RRBS) technique. We examined the relationship between DNAm levels at each CpG site and serum ALT using a linear mixed-effects model. Enrichment analysis and causal inference analysis was conducted, and differentially methylated regions (DMRs) were further identified. Candidate CpGs were validated in a community sample. Genome-wide significance were calculated by Bonferroni correction (p < 2.14 × 10^-7).</p><p><strong>Results: </strong>We identified 85 CpGs reaching genome-wide significance (p < 2.14 × 10^-7), located in 16 genes including FLT4, ADARB2, MRPS31P2, and RELB. Causal inference suggested that DNAm at 61 out of 85 significant CpGs within 14 genes influenced ALT level. 52 DMRs and 1765 pathways such as low voltage-gated calcium channel activity and focal adhesion were identified having influences on ALT levels. Further validation using community population found four CpGs mapped to FLT4 and three to RELB showing hypomethylation and hypermethylation in cases with abnormal ALT (ALT > 40 U/L), respectively.</p><p><strong>Conclusion: </strong>This study identified several differentially methylated CpG sites associated with serum ALT in the Chinese population, particularly within FLT4 and RELB. These findings provide new insights into the epigenetic modifications underlying liver function.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"65"},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962229","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":"Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II).","authors":"Valentin Max Vetter, Kamil Demircan, Jan Homann, Thilo Samson Chillon, Michael Mülleder, Orr Shomroni, Elisabeth Steinhagen-Thiessen, Markus Ralser, Christina M Lill, Lars Bertram, Lutz Schomburg, Ilja Demuth","doi":"10.1186/s13148-025-01863-7","DOIUrl":"10.1186/s13148-025-01863-7","url":null,"abstract":"<p><strong>Background: </strong>Biological age reflects inter-individual differences in biological function and capacity beyond chronological age. DNA methylation age (DNAmA) and its deviation from chronological age, DNAmA acceleration (DNAmAA), which was calculated as residuals of leukocyte cell count adjusted linear regression of DNAmA on chronological age, were used to estimate biological age in this study. Low levels of serum selenium, selenoprotein P (SELENOP), and the selenocysteine-containing glutathione peroxidase 3 (GPx3) are associated with adverse health outcomes and selenium supplementation is discussed as an anti-aging intervention.</p><p><strong>Methods: </strong>In this study, we cross-sectionally analyzed 1568 older participants from the observational Berlin Aging Study II (mean age ± SD: 68.8 ± 3.7 years, 51% women). Serum selenium was measured by total reflection X-ray fluorescence (TXRF) spectroscopy and SELENOP was determined by sandwich ELISA. GPx3 was assessed as part of a proteomics dataset using liquid chromatography-mass spectrometry (LC-MS). The relationship between selenium biomarkers and epigenetic clock measures was analyzed using linear regression analyses. P values and 95% confidence intervals (not adjusted for multiple testing) are stated for each analysis.</p><p><strong>Results: </strong>Participants with deficient serum selenium levels (< 90 μg/L) had a higher rate of biological aging (DunedinPACE, β = - 0.02, SE = 0.01, 95% CI - 0.033 to - 0.004, p = 0.010, n = 865). This association remained statistically significant after adjustment for age, sex, BMI, smoking, and first four genetic principal components (β = - 0.02, SE = 0.01, 95% CI - 0.034 to - 0.004, p = 0.012, n = 757). Compared to the highest quartile, participants in the lowest quartile of SELENOP levels showed an accelerated biological aging rate (DunedinPACE, β = - 0.03, SE = 0.01, 95% CI - 0.051 to - 0.008, p = 0.007, n = 740, fully adjusted model). Similarly, after adjustment for confounders, accelerated biological age was found in participants within the lowest GPx3 quartile compared to participants in the fourth quartile (DunedinPACE, β = - 0.04, SE = 0.01, 95% CI - 0.06 to - 0.02, p = 0.001, n = 674 and GrimAge, β = - 0.98, SE = 0.32, 95% CI - 1.6 to - 0.4, p = 0.002, n = 608). Only the association with GPx3 remained statistically significant after multiple testing correction.</p><p><strong>Conclusion: </strong>Our study suggests that low levels of selenium biomarkers are associated with accelerated biological aging measured through epigenetic clocks. This effect was not substantially changed after adjustment for known confounders.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"62"},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978796","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":"Plasma cell-free DNA methylation profile before afatinib treatment is associated with progression-free and overall survival of patients with epidermal growth factor receptor gene mutation-positive non-small cell lung cancer.","authors":"Mao Fujimoto, Hiroyuki Yasuda, Eri Arai, Makoto Nakajima, Saori Takata, Kei Morikawa, Hisashi Tanaka, Hidetoshi Itani, Takeshi Honda, Kazuya Horiuchi, Kageaki Watanabe, Hideyuki Nakagawa, Yoshiro Nakahara, Yoshitaka Seki, Akihiro Bessho, Nobumasa Takahashi, Kentaro Hayashi, Takeo Endo, Kiyoshi Takeyama, Toshiya Maekura, Nagio Takigawa, Akikazu Kawase, Makoto Endoh, Kenji Nemoto, Kazuma Kishi, Kenzo Soejima, Yusuke Okuma, Akira Togashi, Noriyuki Matsutani, Nobuhiko Seki, Yae Kanai","doi":"10.1186/s13148-025-01870-8","DOIUrl":"https://doi.org/10.1186/s13148-025-01870-8","url":null,"abstract":"<p><strong>Background: </strong>The present study aimed to clarify the clinical significance of the cell-free DNA (cfDNA) methylation profile of patients with non-small cell lung cancer (NSCLC) showing the epidermal growth factor receptor (EGFR) gene mutation.</p><p><strong>Methods: </strong>In 103 patients, genome-wide DNA methylation analysis using Infinium Methylation EPIC array was performed using samples of pre-tyrosine kinase inhibitor afatinib-treatment plasma cfDNA (n = 101) and post-afatinib cfDNA (n = 84).</p><p><strong>Results: </strong>Principal component analysis indicated that the cfDNA methylation profile was altered after afatinib treatment. Hierarchical clustering using the pre-afatinib cfDNA methylation profile revealed that cases with a fatal outcome were accumulated in specific clusters. Moreover, Kaplan-Meier analysis showed that the pre-afatinib cfDNA methylation profile was significantly associated with both progression-free survival (PFS) and overall survival (OS), whereas the post-afatinib profile was not. The genes for which pre-afatinib cfDNA methylation levels were associated with PFS were accumulated in the cadherin, Wnt, and EGFR signaling pathways. Activation of EGFR-related signaling due to DNA methylation alterations might overturn the effect of afatinib. Pre-afatinib levels of CEP170 and CHCHD6 cfDNA methylation were associated with both PFS and OS. Both pre- and post-afatinib cfDNA methylation levels of SLC9A3R2 and INTS1 were associated with bone metastasis. Using the cfDNA methylation levels at two CpG sites, cg12721600 and cg05905155, patients showing an overall response were predicted with a sensitivity of 96% or more.</p><p><strong>Conclusions: </strong>The non-invasively measurable cfDNA methylation profile may reflect the corresponding profile in cancer cells, and that pre-treatment measurement may provide clinically useful information on EGFR mutation-positive NSCLC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"63"},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964270","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":"Applying blood-derived epigenetic algorithms to saliva: cross-tissue similarity of DNA-methylation indices of aging, physiology, and cognition.","authors":"Sepideh Zarandooz, Laurel Raffington","doi":"10.1186/s13148-025-01868-2","DOIUrl":"https://doi.org/10.1186/s13148-025-01868-2","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic algorithms of aging, health, and cognition, based on DNA-methylation (DNAm) patterns, are prominent tools for measuring biological age and have been linked to age-related diseases, cognitive decline, and mortality. While most of these methylation profile scores (MPSs) are developed in blood tissue, there is growing interest in using less invasive tissues like saliva. The aim of the current study is to probe the cross-tissue intraclass correlation coefficients (ICCs) of MPSs developed in blood applied to saliva DNAm from the same people. While our primary focus is on MPSs that were previously found to be robustly correlated with social determinants of health, including second- and third-generation clocks and MPSs of physiology and cognition, we also report ICC values for first-generation clocks to enable comparison across metrics. We pooled three publicly available datasets that had both saliva and blood DNAm from the same individuals (total n = 107, aged 5-74 years), corrected MPSs for cell composition within each tissue, and computed the cross-tissue ICCs.</p><p><strong>Results: </strong>We found that after correcting for cell composition, saliva-blood cross-tissue ICCs were moderate for second- and third-generation indices of aging and MPSs of physiology and cognition. Specifically, PCGrimAge had the highest ICC (0.76), followed by PCPhenoAge (0.72), a measure of cognitive performance (Epigenetic-g, 0.69), DunedinPACE (0.68), PCGrimAge Acceleration (0.67), PCPhenoAge Acceleration (0.66), an MPS of hs-CRP (0.58), and BMI (0.54). These ICCs appear lower than previous reports on within-tissue ICCs (saliva ICCs range from 0.67 to 0.85, blood ICCs range from 0.73 to 0.93). Cross-tissue ICCs values for first-generation biological age acceleration measures were poor, ranging from 0.19 to 0.25.</p><p><strong>Conclusions: </strong>Our findings suggest that applying second- and third-generation MPSs of biological age acceleration and related phenotypes developed in blood to saliva DNAm results in moderate cross-tissue similarity and the precise cross-tissue correspondence differs by measure. While the degree of cross-tissue similarity of several MPSs may suffice for some research settings, it may not be suitable in clinical or commercial applications. Collection of both blood and saliva DNAm samples is necessary to validate existing algorithms and to customize MPSs in saliva DNAm.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"61"},"PeriodicalIF":4.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986037","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 DNA methylation 7 months after SARS-CoV-2 infection.","authors":"Peizhen Hong, Melanie Waldenberger, Michael Pritsch, Leonard Gilberg, Isabel Brand, Jan Bruger, Jonathan Frese, Noemi Castelletti, Mercè Garí, Christof Geldmacher, Michael Hoelscher, Annette Peters, Pamela R Matías-García","doi":"10.1186/s13148-025-01866-4","DOIUrl":"https://doi.org/10.1186/s13148-025-01866-4","url":null,"abstract":"<p><strong>Background: </strong>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and SARS-CoV-2 has been linked to changes in DNA methylation (DNAm) patterns. Studies focused on post-SARS-CoV-2 infection and DNAm have been mainly carried out among severe COVID-19 cases or without distinguishing the severity of cases. However, investigations into mild and asymptomatic cases after SARS-CoV-2 infection are limited. In this study, we analyzed DNAm patterns of mild and asymptomatic cases seven months after SARS-CoV-2 infection in a household setting by conducting epigenome-wide association studies (EWAS).</p><p><strong>Results: </strong>We identified DNAm changes at 42 CpG sites associated with anti-SARS-CoV-2 antibody levels. We additionally report EWAS between COVID-19 cases and controls, with the case status being confirmed by either an antibody test or a PCR test. The EWAS with an antibody test case definition identified 172 CpG sites to be differentially methylated, while the EWAS with a PCR test case definition identified 502 CpG sites. Two common sites, namely cg17126990 (annotated to AFAP1L2) and cg25483596 (annotated to PC), were identified to be hypermethylated across the three EWAS. Both CpG sites have been reported to be involved in molecular pathways after SARS-CoV-2 infection. While AFAP1L2 has been found to be upregulated after SARS-CoV-2 infection, the pyruvate carboxylase (PC) activity seems to be affected by SARS-CoV-2 infection resulting in changes to the host cell metabolism. Additionally, an EWAS to assess persistent health restrictions among PCR-confirmed cases showed 40 CpG sites to be differentially methylated.</p><p><strong>Conclusions: </strong>We detected associations between DNAm in individuals who had asymptomatic and mild SARS-CoV-2 infections as compared to their household controls. These findings contribute to our understanding of the molecular consequences of SARS-CoV-2 infection observed months after infection.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"60"},"PeriodicalIF":4.8,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967071","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}