EpigeneticsPub Date : 2025-12-01Epub Date: 2025-08-04DOI: 10.1080/15592294.2025.2541248
Rundong Liu, Mingjie Liu, Chendong Wang, Zhen Tao, Guangyuan Hu
{"title":"Association of systemic immune-inflammation index (SII) with epigenetic age acceleration in adults: insights from NHANES.","authors":"Rundong Liu, Mingjie Liu, Chendong Wang, Zhen Tao, Guangyuan Hu","doi":"10.1080/15592294.2025.2541248","DOIUrl":"10.1080/15592294.2025.2541248","url":null,"abstract":"<p><p>The Systemic Immune-Inflammation Index (SII), a marker of systemic inflammation, has been linked to various age-related diseases, but its association with Epigenetic Age Acceleration (EAA) remains underexplored. This study aimed to investigate the SII and EAA relationship. We analysed data from 1,915 participants from the National Health and Nutrition Examination Survey (NHANES). SII was calculated as platelet count × (neutrophil count/lymphocyte count). EAA was defined as HorvathAccel, HannumAccel, Skin&BloodAccel, PhenoAgeAccel, GrimAge2Accel, and DunedinPoAm. These metrics were derived utilizing the residual method. Multivariate linear regression, smooth curve fitting, threshold effect analyses, and subgroup analyses were employed to assess the relationship between the SII and EAA. Higher SII levels were significantly associated with HannumAccel, PhenoAgeAccel, GrimAge2Accel, and DunedinPoAm. Threshold effect analyses revealed non-linear relationships, with inflection points at SII values of 24.200, 12.553, 7.766, and 10.133, respectively. Subgroup analyses identified sex, age, poverty-to-income ratio, and marital status as significant effect modifiers. The elevated SII was associated with accelerated epigenetic ageing.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2541248"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-07-03DOI: 10.1080/15592294.2025.2527145
Jiawei Li, Wanjun Luo, Daohong Nie, Zidan Lin, Chenfei Zhou
{"title":"Mendelian randomization analysis of CpG methylation and immune phenotypes in epithelial ovarian cancer outcomes.","authors":"Jiawei Li, Wanjun Luo, Daohong Nie, Zidan Lin, Chenfei Zhou","doi":"10.1080/15592294.2025.2527145","DOIUrl":"10.1080/15592294.2025.2527145","url":null,"abstract":"<p><p>Epithelial ovarian cancer (EOC) is a heterogeneous malignancy with distinct histological subtypes, and DNA methylation has emerged as a promising biomarker for early detection. However, the role of methylation patterns in EOC heterogeneity and prognosis remains unclear. In this study, genome-wide association studies (GWAS) data from the Ovarian Cancer Association Consortium (OCAC) and Methylation quantitative trait loci (mQTL) data from the Genetics of DNA Methylation Consortium (GoDMC) were analysed using two-sample Mendelian randomization (MR). We investigated the genetic effects of CpG methylation on the risk and prognosis of five major EOC histotypes. To further explore the mechanisms by which DNA methylation affects EOC outcomes, we performed mediation analysis to evaluate the role of immunophenotypes. Our analysis identified 94 CpG sites associated with high-grade serous ovarian cancer (HGSOC), 9 of which were linked to prognosis. Additional significant associations were found for clear cell, low-grade serous, endometrioid, and mucinous subtypes. Hypomethylation at specific CpG sites was linked to increased EOC risk and shorter survival. Mediation analysis revealed significant interactions between CpG methylation and immunophenotypes, suggesting that immune modulation mediates the effects of DNA methylation on EOC outcomes. These results provide novel insights into the importance of epigenetic and immune-related factors in EOC pathogenesis.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2527145"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-02-20DOI: 10.1080/15592294.2025.2469205
Lisha Lin, Wei Zhao, Zheng Li, Scott M Ratliff, Yi Zhe Wang, Colter Mitchell, Jessica D Faul, Sharon L R Kardia, Kira S Birditt, Jennifer A Smith
{"title":"Poly-epigenetic scores for cardiometabolic risk factors interact with demographic factors and health behaviors in older US Adults.","authors":"Lisha Lin, Wei Zhao, Zheng Li, Scott M Ratliff, Yi Zhe Wang, Colter Mitchell, Jessica D Faul, Sharon L R Kardia, Kira S Birditt, Jennifer A Smith","doi":"10.1080/15592294.2025.2469205","DOIUrl":"10.1080/15592294.2025.2469205","url":null,"abstract":"<p><p>Poly-epigenetic scores (PEGS) are surrogate measures that help capture individual-level risk. Understanding how the associations between PEGS and cardiometabolic risk factors vary by demographics and health behaviors is crucial for lowering the burden of cardiometabolic diseases. We used results from established epigenome-wide association studies to construct trait-specific PEGS from whole blood DNA methylation for systolic and diastolic blood pressure (SBP, DBP), body mass index (BMI), C-reactive protein (CRP), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), triglycerides (TG), and fasting glucose. Overall and race-stratified associations between PEGS and corresponding traits were examined in adults >50 years from the Health and Retirement Study (<i>n</i> = 3,996, mean age = 79.5 years). We investigated how demographics (age, sex, educational attainment) and health behaviors (smoking, alcohol consumption, physical activity) modified these associations. All PEGS were positively associated with their corresponding cardiometabolic traits (<i>p</i> < 0.05), and most associations persisted across all racial/ethnic groups. Associations for BMI, HDL-C, and TG were stronger in younger participants, and BMI and HDL-C associations were stronger in females. The CRP association was stronger among those with a high school degree. Finally, the HDL-C association was stronger among current smokers. These findings support PEGS as robust surrogate measures and suggest the associations may differ among subgroups.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2469205"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-02-20DOI: 10.1080/15592294.2025.2466382
Batbayar Khulan, Kenny Ye, Miao Kevin Shi, Spencer Waldman, Ava Marsh, Taha Siddiqui, Aham Okorozo, Aditi Desai, Dhruv Patel, Jay Dobkin, Ali Sadoughi, Chirag Shah, Shweta Gera, Yakov Peter, Will Liao, Jan Vijg, Simon D Spivack
{"title":"Normal bronchial field basal cells show persistent methylome-wide impact of tobacco smoking, including in known cancer genes.","authors":"Batbayar Khulan, Kenny Ye, Miao Kevin Shi, Spencer Waldman, Ava Marsh, Taha Siddiqui, Aham Okorozo, Aditi Desai, Dhruv Patel, Jay Dobkin, Ali Sadoughi, Chirag Shah, Shweta Gera, Yakov Peter, Will Liao, Jan Vijg, Simon D Spivack","doi":"10.1080/15592294.2025.2466382","DOIUrl":"10.1080/15592294.2025.2466382","url":null,"abstract":"<p><p>Lung carcinogenesis is causally linked to cigarette smoking, in part by epigenetic changes. We tested whether accumulated epigenetic change in smokers is apparent in bronchial basal cells as cells of origin of squamous cell carcinoma. Using an EM-seq platform covering 53.8 million CpGs (96% of the entire genome) at an average of 7.5 sequencing reads per CpG site at a single base resolution, we evaluated cytology-normal basal cells bronchoscopically brushed from the in situ tobacco smoke-exposed 'bronchial epithelial field' and isolated by short-term primary culture from 54 human subjects. We found that mean methylation was globally lower in ever (former and current) smokers versus never smokers (<i>p</i> = 0.0013) across promoters, CpG shores, exons, introns, 3'-UTRs, and intergenic regions, but not in CpG islands. Among 6mers with dinucleotides flanking CpG, those containing CGCG showed no effect from smoking, while those flanked with TT and AA displayed the strongest effects. At the gene level, smoking-related differences in methylation level were observed in <i>CDKL1, ARTN</i>, <i>EDC3</i>, <i>CYP1B1</i>, <i>FAM131A</i>, and <i>MAGI2</i>. Among candidate cancer genes, smoking reduced the methylation level in <i>KRAS</i>, <i>ROS1</i>, <i>CDKN1A</i>, <i>CHRNB4</i>, and <i>CADM1</i>. We conclude that smoking reduces long-term epigenome-wide methylation in bronchial stem cells, is impacted by the flanking sequence, and persists indefinitely beyond smoking cessation.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2466382"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-01-18DOI: 10.1080/15592294.2024.2445447
Wei Zhao, Lisha Lin, Kristen M Kelly, Lauren A Opsasnick, Belinda L Needham, Yongmei Liu, Srijan Sen, Jennifer A Smith
{"title":"Epigenome-wide association study of perceived discrimination in the Multi-Ethnic Study of Atherosclerosis (MESA).","authors":"Wei Zhao, Lisha Lin, Kristen M Kelly, Lauren A Opsasnick, Belinda L Needham, Yongmei Liu, Srijan Sen, Jennifer A Smith","doi":"10.1080/15592294.2024.2445447","DOIUrl":"10.1080/15592294.2024.2445447","url":null,"abstract":"<p><p>Perceived discrimination, recognized as a chronic psychosocial stressor, has adverse consequences on health. DNA methylation (DNAm) may be a potential mechanism by which stressors get embedded into the human body at the molecular level and subsequently affect health outcomes. However, relatively little is known about the effects of perceived discrimination on DNAm. To identify the DNAm sites across the epigenome that are associated with discrimination, we conducted epigenome-wide association analyses (EWAS) of three discrimination measures (everyday discrimination, race-related major discrimination, and non-race-related major discrimination) in 1,151 participants, including 565 non-Hispanic White, 221 African American, and 365 Hispanic individuals, from the Multi-Ethnic Study of Atherosclerosis (MESA). We conducted both race/ethnicity-stratified analyses as well as trans-ancestry meta-analyses. At false discovery rate of 10%, 7 CpGs and 4 differentially methylated regions (DMRs) containing 11 CpGs were associated with perceived discrimination exposures in at least one racial/ethnic group or in meta-analysis. Identified CpGs and/or nearby genes have been implicated in cellular development pathways, transcription factor binding, cancer and multiple autoimmune and/or inflammatory diseases. Of the identified CpGs (7 individual CpGs and 11 within DMRs), two CpGs and one CpG within a DMR were associated with expression of cis genes <i>NDUFS5</i>, <i>AK1RIN1</i>, <i>NCF4</i> and <i>ADSSL1</i>. Our study demonstrated the potential influence of discrimination on DNAm and subsequent gene expression.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2445447"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-06-05DOI: 10.1080/15592294.2025.2506625
Rebekka Roth, Margareta Häckh, Tilman Schnick, Carolin Rommel, Christoph Koentges, Heiko Bugger, Claudia Domisch, Michael R Bristow, Amrut V Ambardekar, Timothy A McKinsey, Ralf Gilsbach, Lutz Hein, Sebastian Preissl
{"title":"Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors.","authors":"Rebekka Roth, Margareta Häckh, Tilman Schnick, Carolin Rommel, Christoph Koentges, Heiko Bugger, Claudia Domisch, Michael R Bristow, Amrut V Ambardekar, Timothy A McKinsey, Ralf Gilsbach, Lutz Hein, Sebastian Preissl","doi":"10.1080/15592294.2025.2506625","DOIUrl":"10.1080/15592294.2025.2506625","url":null,"abstract":"<p><p>Fibrosis, cardiac remodelling, and inflammation are hallmarks of heart failure. To date, there is no available pharmacological cure for heart failure, but mechanical unloading by implantation of a left ventricular assist device (LVAD) can lead to improved cardiac function in a subset of patients. This study aimed to identify the transcriptional response of left ventricular (LV) cardiac myocytes to mechanical unloading in a mouse model of reversible LV pressure overload and in failing human hearts after LVAD implantation. We found that partial recovery of ventricular dysfunction, LV hypertrophy, and gene expression programmes occurred in mice under reversible transverse aortic constriction (rTAC). Gene expression analysis in cardiac myocytes identified a lasting repression of mitochondrial gene expression resulting in compromised fatty acid oxidation in the mouse model of reversible pressure overload and in human LV samples after LVAD therapy and a persistent upregulation of epigenetic and transcriptional regulators. These findings underpin that recovery from heart failure involves complex gene regulatory networks and that mitochondrial dysfunction remains a challenge even after mechanical unloading. Further studies are needed to investigate the functional role of these factors in reverse remodelling and recovery of failing hearts.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2506625"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-09-29DOI: 10.1080/15592294.2025.2567459
Jessica Townsend, Mehmet Kizilaslan, Zeynep Kizilaslan, Todd Taylor, Hasan Khatib
{"title":"Epigenetic remodeling of sheep oocytes and embryos induced by maternal methionine supplementation.","authors":"Jessica Townsend, Mehmet Kizilaslan, Zeynep Kizilaslan, Todd Taylor, Hasan Khatib","doi":"10.1080/15592294.2025.2567459","DOIUrl":"10.1080/15592294.2025.2567459","url":null,"abstract":"<p><p>Environmental factors can influence gene expression and developmental outcomes through epigenetic modifications. Although maternal diet influences offspring DNA methylation and phenotypes, its effects on the oocyte and the resulting embryonic epigenome remain poorly understood. Here, we investigated the effect of maternal methionine supplementation on DNA methylation patterns in oocytes and embryos in Polypay sheep. Whole-genome bisulfite sequencing (WGBS) was performed on oocytes collected from 16 twin ewe pairs (8 methionine-treated and 8 controls). These ewes were later bred to control rams, and embryos were flushed for WGBS as well. In oocytes, 2,056 differentially methylated cytosines (DMCs) were identified. Additionally, 17 mitochondrial DMCs were identified, with 12 hypermethylated and 5 hypomethylated. In embryos, 113 DMCs were identified. Mitochondrial DNA analysis revealed 22 hypermethylated DMCs. To assess the inheritance of methyl marks, we compared DMCs between oocytes and embryos. While no direct overlaps were found in nuclear DNA, 3 CpGs exhibited opposite methylation trends - hypomethylated in oocytes but hypermethylated in embryos. In contrast, 5 mitochondrial DMCs overlapped between oocytes and embryos. To functionally assess the role of differentially methylated genes, we performed siRNA-mediated knockdown of 2 embryo DMC-associated genes: <i>SCRIB</i> and <i>CERS3</i>. Knockdown of <i>SCRIB</i> led to a 16.4% average decrease in blastocyst formation rate (<i>p</i> = 0.001), while <i>CERS3</i> knockdown resulted in a 9.5% decrease (<i>p</i> = 0.005). These results demonstrate that maternal methionine supplementation alters nuclear and mitochondrial DNA methylation in oocytes and embryos, and that affected genes may play critical roles in early embryonic development, contributing to fetal programming.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2567459"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-10-29DOI: 10.1080/15592294.2025.2578552
O Emery, C Carmeli, S Gonseth-Nusslé, Rp Juster, C Kinnaer, D Nanchen, S Nusslé, S Stringhini, Jd Chamberlain
{"title":"Integrative DNA methylation and transcriptome analysis reveal cell-type specific patterns in response to elevated allostatic load.","authors":"O Emery, C Carmeli, S Gonseth-Nusslé, Rp Juster, C Kinnaer, D Nanchen, S Nusslé, S Stringhini, Jd Chamberlain","doi":"10.1080/15592294.2025.2578552","DOIUrl":"10.1080/15592294.2025.2578552","url":null,"abstract":"<p><p>Allostatic load (AL) is a measure of the body's multi-systemic physiological dysregulation in response to chronic stress and life events. High AL has been associated with poor long-term health outcomes such as cardiovascular disease and mortality. DNA methylation (DNAm) is an epigenetic mechanism involving both genes and environmental factors and contributes to gene expression regulation. Hence, changes in AL can possibly be reflected in DNAm and gene expression differences and leveraging epigenetic and transcriptomic data together can help elucidate the underlying biological processes involved. To assess differential DNAm and gene expression between high and low AL in a cell-type specific manner, bulk DNAm and transcriptome signals from whole blood samples of 429 individuals from the Swiss Kidney Project On Genes in Hypertension (SKIPOGH) cohort were first deconvoluted into cell-type specific signals for six blood cell types using tensor composition analysis (TCA) and the software CIBERSORTx. For each cell type, DNAm associated with gene expression changes was then determined in high (<i>N</i> = 126) vs low (<i>N</i> = 303) AL groups. A total of 263 CpG-gene pairs were identified across all cell types, corresponding to 250 unique CpGs and 138 unique differentially methylated genes (DMGs). Several immune processes were enriched among downregulated genes of CD8 T and B cells, suggesting an impairment of the immune response, which is compatible with high AL. These findings highlight the importance of using cell-specific signals in DNAm and transcriptome analyses and may contribute to identify AL biomarkers and/or potential therapeutic targets.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2578552"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145388235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci.","authors":"Yue Huo, Yaru Gao, Jiayi Ruan, Lingli Wang, Hongdong Li, Guini Hong","doi":"10.1080/15592294.2025.2487316","DOIUrl":"10.1080/15592294.2025.2487316","url":null,"abstract":"<p><p>Skin cutaneous melanoma (SKCM) is an aggressive tumor with a poor prognosis. We developed SKCM-P8, a novel qualitative prognostic biomarker based on the relative methylation orderings of eight pairs of loci. Analysis of a training cohort and two independent validation datasets revealed a significant difference in overall survival between high- and low-risk groups stratified by SKCM-P8 (<i>p</i> < 0.05, log-rank test), with average area under the curve values of 0.83, 0.80, and 0.61, respectively. The differential methylation loci between high- and low-risk patients were enriched in immune-related biological processes and signaling pathways. Furthermore, low-risk patients exhibited higher CD8+ T cells and B levels, while high-risk patients had higher monocytes. The methylation levels of SKCM-P8 were also correlated with immune cell levels, indicating that they can reflect prognosis-related immune information. The low-risk group had a significantly higher mutation burden (<i>p</i> < 0.05, Wilcoxon test), suggesting potential benefits from immune checkpoint inhibitors. Patients stratified by SKCM-P8 displayed differential responses to therapy and immunotherapy (<i>p</i> < 0.05, Wilcoxon test), with low-risk patients showing better sensitivity and response. Furthermore, SKCM-P8 demonstrated super-predictive accuracy compared to six published models. Overall, SKCM-P8 offers a promising tool for predicting prognosis and guiding therapeutic decisions in SKCM.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2487316"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-02-25DOI: 10.1080/15592294.2025.2471129
Allison A Appleton
{"title":"A polyepigenetic glucocorticoid exposure score and HPA axis-related DNA methylation are associated with gestational epigenetic aging.","authors":"Allison A Appleton","doi":"10.1080/15592294.2025.2471129","DOIUrl":"10.1080/15592294.2025.2471129","url":null,"abstract":"<p><p>Gestational epigenetic aging (GEA) is a novel approach for characterizing associations between prenatal exposures and postnatal risks. Psychosocial adversity in pregnancy may influence GEA, but the molecular mechanisms are not well understood. DNA methylation to glucocorticoid regulation and hypothalamic-pituitary-adrenal (HPA) axis genes are implicated but have not been fully examined in association with GEA. This study investigated whether a polyepigenetic glucocorticoid exposure score (PGES) and HPA axis gene (<i>NR3C1, HSD11B2, FKBP5</i>) methylation were associated with GEA, and whether associations were sex-specific. Participants were from a prospective cohort of racial/ethnic diverse and socially disadvantaged pregnant women and infants (<i>n</i> = 200). DNA methylation variables were estimated using umbilical cord blood. PGES was derived with CpGs shown to be sensitive to synthetic dexamethasone exposure. <i>NR3C1</i>, <i>HSD11B2</i>, and <i>FKBP5</i> methylation was summarized via factor analysis. We found that PGES (β = -1.12, SE = 0.47, <i>p</i> = 0.02) and several <i>NR3C1</i> and <i>FKBP5</i> factor scores were associated with decelerated GEA (all <i>p</i> < 0.05). A significant sex interaction was observed for <i>FKBP5</i> factor score 3 (β = -0.34, SE = 0.15, <i>p</i> = 0.02) suggesting decelerated GEA for males but not females. This study showed that glucocorticoid regulation-related DNA methylation was associated with a decelerated aging phenotype at birth that might indicate a neonatal risk.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2471129"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}