Clinical Epigenetics最新文献

{"title":"SERPINA1 methylation as a novel diagnostic marker for early-stage papillary thyroid carcinoma via MAPK6-AKT/mTOR pathway.","authors":"Junjie Li, Haixia Huang, Yifei Yin, Yizhu Mao, Mengxia Li, Hong Li, Chenxia Jiang, Rongxi Yang","doi":"10.1186/s13148-025-01891-3","DOIUrl":"https://doi.org/10.1186/s13148-025-01891-3","url":null,"abstract":"<p><p>Most thyroid nodules can be diagnosed preoperatively by ultrasonography and fine-needle aspiration biopsy. However, accurately differentiating between benign nodules or indolent thyroid tumors and aggressive thyroid cancers remains a significant clinical challenge when the biopsy results are indeterminate. In this study, we aim to explore a novel biomarker to determine the malignancy of thyroid nodules. Fifteen tissue samples from patients with Stage I&II papillary thyroid carcinoma (PTC) and benign thyroid nodule (BTN) were analyzed by EPIC Methylation 850 K and RNA-Sequencing. Altered and inversely correlated methylation and expression in SERPINA1 gene in PTC was found in the discovery study. PTC-associated SERPINA1 hypomethylation was further verified by mass spectrometry in case-control studies from two clinical centers (Validation I: 140 PTCs vs. 182 BTNs, ORs ≥ 2.48, and Validation II: 224 PTCs vs. 217 BTNs, ORs ≥ 2.04; P ≤ 3.07E-15, for all measurable CpG sites). Moreover, SERPINA1 methylation had an outstanding clinical application value to differentiate PTC from BTN (the AUC combining Validation I and Validation II was 0.92). Our study also revealed that the upregulated SERPINA1 could promote cell proliferation, migration and invasion in the PTC cell lines, and thereby facilitate the malignant progression of PTC. Mechanistically, SERPINA1 activated the AKT/mTOR pathway via binding to MAPK6. Intervention targeting either SERPINA1 or MAPK6 has a significant impact on the malignancy of PTC cells. Together, we identified SERPINA1 methylation as a functional and effective diagnostic marker for PTC and provided a novel epigenetic insight into the etiology of PTC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"86"},"PeriodicalIF":4.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180437","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":"Sleep patterns and DNA methylation age acceleration in middle-aged and older Chinese adults.","authors":"Tingyue Diao, Kang Liu, Lue Zhou, Qiuhong Wang, Junrui Lyu, Ziwei Zhu, Fuchao Chen, Wengang Qin, Handong Yang, Chaolong Wang, Xiaomin Zhang, Tangchun Wu","doi":"10.1186/s13148-025-01898-w","DOIUrl":"https://doi.org/10.1186/s13148-025-01898-w","url":null,"abstract":"<p><strong>Background: </strong>Sleep is a biological necessity and fundamental to health. However, the associations of sleep patterns (integrating sleep determinants) with DNA methylation age acceleration (DNAm AA) remain unknown. We aimed to investigate the associations of sleep patterns with DNAm AA.</p><p><strong>Methods: </strong>This cross-sectional and prospective cohort study used data from the Dongfeng-Tongji cohort collected from 2013 to December 31, 2018. Sleep patterns were reflected by sleep scores (range 0-4, with higher scores indicating healthier sleep patterns) characterized by bedtime, sleep duration, sleep quality, and midday napping. DNAm AA was estimated by PhenoAge acceleration (PhenoAgeAccel), GrimAge acceleration (GrimAgeAccel), DunedinPACE, and DNAm mortality risk score (DNAm MS). Linear regression models were used to estimate β and 95% confidence intervals (CIs) for the cross-sectional associations between sleep patterns and DNAm AA. Mediation models were applied to assess the mediating role of DNAm AA in the associations between sleep patterns and all-cause mortality in a prospective cohort.</p><p><strong>Results: </strong>Among 3566 participants (mean age 65.5 years), 426 participants died during a mean 5.4-year follow-up. A higher sleep score was associated with lower DNAm AA in a dose-response manner. Each 1-point increase in sleep score was associated with significantly lower PhenoAgeAccel (β = - 0.208; 95% CI - 0.369 to - 0.047), GrimAgeAccel (β = - 0.107; 95% CI - 0.207 to - 0.007), DunedinPACE (β = - 0.008; 95% CI - 0.012 to - 0.004), and DNAm MS (β = - 0.019; 95% CI - 0.030 to - 0.008). Chronological age modified the associations between higher sleep scores and lower PhenoAgeAccel (p for interaction = 0.031) and DunedinPACE (p for interaction = 0.027), with stronger associations observed in older adults. Moreover, a slower DunedinPACE mediated 6.2% (95% CI 0.8% to 11.5%) of the association between a higher sleep score and a lower all-cause mortality risk.</p><p><strong>Conclusion: </strong>In this cohort study, individuals with a higher sleep score had a slower DNAm AA, particularly in older adults. A slower DunedinPACE partially explained the association between higher sleep scores and lower all-cause mortality risk. These findings suggest that adopting healthy sleep patterns may promote healthy aging and further benefit premature mortality prevention, highlighting the value of sleep patterns as a potential tool for clinical management in aging.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"87"},"PeriodicalIF":4.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180977","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":"H3K18 lactylation-mediated Ythdf2 activation restrains mouse female germline stem cell proliferation via promoting Ets1 mRNA degradation.","authors":"Yunqiang Wu, Bo Xu, Yonglin Peng, Sang Lin, Wenfei Du, Ruiqi Liu, Shu Zhang, Ji Wu, Kang Zou, Xiaodong Zhao","doi":"10.1186/s13148-025-01890-4","DOIUrl":"https://doi.org/10.1186/s13148-025-01890-4","url":null,"abstract":"<p><strong>Background: </strong>Germline stem cells are critical for sustaining fertility by balancing self-renewal and differentiation, and are regulated by genetic and epigenetic programs. Although extensively investigated, the rare female germline stem cells (FGSCs) in mammalian ovaries hinder their application in regenerative medicine. The N⁶-methyladenosine (m⁶A) reader YTHDF2 is required for female germ cell competence. However, the mechanistic underpinnings of how YTHDF2 regulates FGSC proliferation remain elusive.</p><p><strong>Results: </strong>Here, we show that knockout of Ythdf2 enhances FGSC proliferation in vitro. YTHDF2 binds m⁶A-modified Ets1 mRNA and facilitates its degradation in an m⁶A-dependent manner. ETS1 functions as a key downstream effector of YTHDF2, as suppression of ETS1 expression partially reverses the Ythdf2-KO-induced phenotype. Additionally, we demonstrate that YTHDF2/ETS1 axis participates in regulating FGSC proliferation by modulation of proliferation-related gene expression. Moreover, histone lactylation modification H3K18la activates the expression of YTHDF2 in FGSCs.</p><p><strong>Conclusions: </strong>Overall, our study reveals that YTHDF2 intrinsically restrains mouse FGSC proliferation and provides a potential strategy to increase FGSC abundance for its potential clinical application.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"84"},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157135","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":"Cadmium exposure, epigenetic modifications, and serum cystatin C: insights into mediated pathways and mortality risks in U.S. adults.","authors":"Yu-Wei Fang, Ching-Way Chen, Ta-Chen Su, Chien-Yu Lin","doi":"10.1186/s13148-025-01888-y","DOIUrl":"10.1186/s13148-025-01888-y","url":null,"abstract":"<p><strong>Background: </strong>Cadmium exposure has been linked to elevated cystatin C levels, disruptions in epigenetic patterns, and increased mortality risk. However, the role of epigenetic modifications in the relationship between cadmium and cystatin C remains poorly understood. Furthermore, it is unclear how cystatin C and epigenetic changes influence the connection between cadmium exposure and mortality outcomes. The study explored the associations among blood cadmium levels, serum cystatin C, an epigenetic biomarker (DNA methylation-predicted cystatin C, DNAmCystatinC), and mortality outcomes.</p><p><strong>Methods: </strong>We utilized data from 8716 participants aged 18 years and older in the National Health and Nutrition Examination Survey (NHANES, 1999-2002), linked to mortality records from the National Center for Health Statistics (NCHS) through 2019.</p><p><strong>Results: </strong>Our findings revealed that higher natural log-transformed (ln)-blood cadmium was associated with elevated ln-serum cystatin C (β = 0.052, P < 0.001) and higher ln-DNAmCystatinC (β = 0.007, P = 0.008). Compared to the reference group (both blood cadmium and DNAmCystatinC ≤ 50th percentile), those with blood cadmium and DNAmCystatinC > 50th percentile had the highest mean serum cystatin C levels (1.26 mg/L vs. 1.11 mg/L; P for trend = 0.002). Structural equation modeling (SEM) indicated that DNAmCystatinC partially mediated the relationship between cadmium exposure and cystatin C, with a total effect of 0.068, a direct effect of 0.066, and an indirect effect of 0.002. Weighted Cox regression analysis showed higher blood cadmium was associated with an increased risk of all mortality outcomes, with stronger associations observed in individuals whose serum cystatin C was at or above the 50th percentile. These findings were consistent both in the overall population and after excluding individuals with chronic kidney disease. Furthermore, a significant interaction was identified between blood cadmium and serum cystatin C in their influence on all-cause mortality.</p><p><strong>Conclusions: </strong>We found higher blood cadmium is linked to increased serum cystatin C and DNAmCystatinC, with DNAmCystatinC partially mediating the effect on serum cystatin C. Notably, serum cystatin C may modify the relationship between cadmium exposure and mortality outcomes. Further research is warranted to elucidate these complex interactions.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"85"},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157134","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":"Allelic expression patterns of imprinted and non-imprinted genes in cancer cell lines from multiple histologies.","authors":"Julia Krushkal, Travis L Jensen, George Wright, Yingdong Zhao","doi":"10.1186/s13148-025-01883-3","DOIUrl":"10.1186/s13148-025-01883-3","url":null,"abstract":"<p><strong>Background: </strong>Imprinted genes are epigenetically regulated in normal tissues to follow monoallelic expression according to the parent of origin of each allele. Some of these patterns are dysregulated in cancer.</p><p><strong>Results: </strong>We developed a novel computational multi-omic pipeline to evaluate monoallelic and biallelic expression patterns based on matched RNA-seq expression data, whole-exome sequencing information, and copy number data. We analyzed allelic expression of the entire genes, individual isoforms, and each exon of 59,283 autosomal protein-coding and ncRNA genes, with a focus on 94 genes previously reported to be imprinted. We analyzed 108 cell lines from 9 different tumor histologies using molecular data from the DepMap Portal for the Cancer Cell Line Encyclopedia. Allelic expression patterns of imprinted genes and isoforms in tumor cells were variable. We also identified additional genes and isoforms with predominantly monoallelic expression due to a variety of potential mechanisms. We provide a novel public dataset of transcriptome-wide allelic expression patterns in cell lines from diverse tumor categories, which can serve as a resource for future cancer studies. We examined associations of in vitro cell line response to antitumor agents and repurposed drugs with allelic patterns and overall levels of isoform expression of imprinted genes and of additional genes with predominantly monoallelic expression. Drug response was associated with isoform expression patterns of multiple imprinted genes including CPA4, DGCR6, DNMT1, GNAS, GRB10, H19, NAA60, OSBPL5, PHACTR2, and ZFAT, predominantly monoallelically expressed MAP2K5 and BCLAF1, and additional predominantly monoallelically expressed genes. Multiple associations may be related to mechanisms of drug activity, including associations between the response to the DNA damaging agents and allelic expression of ZFAT, CDC27, and BCLAF1 isoforms, and the response to inhibitors of multiple signaling pathways with expression patterns of GNAS isoforms.</p><p><strong>Conclusions: </strong>Tumor cells have a range of monoallelic and biallelic expression patterns in both imprinted and non-imprinted genes and are likely affected by the complex interplay among changes in allelic expression, sequence variants, copy number changes, and expression changes of biologically important genes. Multiple isoform-specific patterns of allelic expression were associated with drug response, indicating complex mechanisms of cancer chemoresistance.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"83"},"PeriodicalIF":4.8,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141597","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 hypermethylation of PLTP mediated by DNMT3B aggravates vascular dysfunction in diabetic retinopathy via the AKT/GSK3β signaling pathway.","authors":"Chunyang Cai, Chufeng Gu, Chunren Meng, Yujie Wang, Qingquan Wei, Shuai He, Dongwei Lai, Xingyun Wang, Tengfei Wang, Qinghua Qiu","doi":"10.1186/s13148-025-01874-4","DOIUrl":"10.1186/s13148-025-01874-4","url":null,"abstract":"<p><strong>Background: </strong>This study aims to elucidate the effect and mechanism of phospholipid transfer protein (PLTP) on vascular dysfunction in DR and explore the molecular mechanism of abnormal PLTP expression based on DNA methylation.</p><p><strong>Methods: </strong>Human retinal microvascular endothelial cells (HRMECs) cultured in high glucose (HG) and streptozotocin-treated mice were used as DR models to detect and screen the key genes with abnormal promoter DNA methylation. Single-cell sequencing, tube formation and migration assays were employed to verify the relationship between PLTP and vascular function. Additionally, siRNA and luciferase reporter assay were used to study the key enzymes regulating the DNA methylation of PLTP. Transcriptome sequencing, coimmunoprecipitation and GSK3β inhibitor were utilized to identify and validate the key downstream pathways of PLTP.</p><p><strong>Results: </strong>DR models exhibited DNA hypermethylation and decreased expression of PLTP. Abnormal PLTP expression was implicated in vascular dysfunction, and PLTP overexpression reversed HG-induced effects on the migration and tube formation of endothelial cells. The siDNMT3B and luciferase reporter assay indicated that DNMT3B is the primary enzyme affecting abnormal methylation. Interestingly, PLTP promoted the phosphorylation of AKT and GSK3β, indicating that PLTP modulates angiogenesis via the AKT/GSK3β signaling pathway.</p><p><strong>Conclusions: </strong>PLTP regulates the proliferation, migration and tube formation of HRMECs, and is involved in maintaining vascular function via the AKT/GSK3β signaling pathway. In HG environment, increased DNMT3B expression upregulates DNA methylation of the PLTP promoter, downregulating PLTP expression and leading to vascular dysfunction in DR.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"82"},"PeriodicalIF":4.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086099","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":"Unveiling the impact of DNA-methylation age acceleration on mortality risk in diabetes and pre-diabetes: insights from the US NHANES program.","authors":"Shuang Wu, Ziyi Zhong, Yimeng Wang, Jingyang Wang, Siqi Lyu, Hongyu Liu, Yang Chen","doi":"10.1186/s13148-025-01886-0","DOIUrl":"10.1186/s13148-025-01886-0","url":null,"abstract":"<p><strong>Background: </strong>Diabetes ranks as the ninth leading cause of death globally, and DNA-methylation age acceleration (DNAmAA) is closely linked to lifespan. However, the impact of DNAmAA on long-term outcomes in specific populations with diabetes and pre-diabetes has not yet been comprehensively studied.</p><p><strong>Methods: </strong>This retrospective cohort study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, including participants aged 20 years or older diagnosed with diabetes or pre-diabetes. DNAmAA was defined as the difference between epigenetic age and chronological age. Multiple generations of DNAmAA measures were included. Cox proportional hazards regression models were employed to estimate the associations between DNAmAAs and all-cause, cardiovascular, and non-cardiovascular mortality.</p><p><strong>Results: </strong>A total of 1,199 participants were included, with a mean age of 64.20 (0.46) years; 621 (51.8%) were male. Significant correlations were observed between chronological age and all DNA-methylation ages in both diabetes and pre-diabetes groups. Over a mean follow-up of 14.13 (5.90) years, 662 deaths were recorded. AgeAccelGrim2 exhibited the strongest association with mortality. Each 5-unit increase in AgeAccelGrim2 was associated with an elevated risk of all-cause mortality (HR 1.35, 95% CI 1.23-1.49), cardiovascular mortality (HR 1.50, 95% CI 1.25-1.80), and non-cardiovascular mortality (HR 1.30, 95% CI 1.16-1.46). These associations remained significant in participants with diabetes and pre-diabetes. Mediation analysis revealed that AgeAccelGrim2 significantly mediates the association between health-related exposures (including the Oxidative Balance Score, Life's Simple 7 score, and frailty score) and all-cause mortality in diabetes and pre-diabetes populations.</p><p><strong>Conclusions: </strong>AgeAccelGrim2 could serve as a valuable biomarker for mortality risk specific to populations with diabetes and pre-diabetes, offering potential applications in personalized management strategies and risk stratification.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"81"},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086114","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 of epigenetic aging with self-rated health, access to care, and healthcare utilization in a representative sample of United States adults.","authors":"Jamaji C Nwanaji-Enwerem, Dennis Khodasevich, Nicole Gladish, Hanyang Shen, Anne K Bozack, Saher Daredia, Belinda L Needham, David H Rehkopf, Andres Cardenas","doi":"10.1186/s13148-025-01887-z","DOIUrl":"https://doi.org/10.1186/s13148-025-01887-z","url":null,"abstract":"<p><strong>Background: </strong>Health status is closely linked to both healthcare access and utilization. While previous research has identified associations between health status and DNA methylation-based biomarkers of aging (epigenetic aging), studies exploring these relationships in the context of healthcare access and utilization remain limited. To address this gap, we analyzed cross-sectional associations in a representative sample of 2,343 U.S. adults from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition Examination Survey (NHANES). Our study examined the relationships of self-rated health status, healthcare access, and healthcare utilization with seven epigenetic aging biomarkers: HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge2, DNAm Telomere Length (DNAmTL), and DunedinPoAm.</p><p><strong>Results: </strong>After adjusting for chronological age, demographics, lifestyle factors, and health insurance, participants with good-excellent self-rated health had a 1.58-year lower PhenoAge (95% CI - 2.54, - 0.62 P = 0.006) and a 1.16-year lower GrimAge2 (95% CI - 1.80, - 0.53, P = 0.004) than participants with poor-fair health. Participants who reported having a routine place where they received healthcare had a lower GrimAge2 (β = - 1.44-years, 95% CI - 2.66, - 0.22, P = 0.03) than participants without a routine healthcare location. Participants with ≥ 10 healthcare visits in the prior year had a shorter DNAmTL (β = - 0.05-kb, 95% CI - 0.09, - 0.01, P = 0.02) than participants with < 10 visits. After including additional adjustments for estimated leukocyte proportions, participants who were hospitalized overnight in the prior year had a shorter DNAmTL (β = - 0.05-kb, 95% CI - 0.08, - 0.01, P = 0.02) than non-hospitalized individuals.</p><p><strong>Conclusions: </strong>Our findings reinforce previous reports linking better health status to lower epigenetic aging and provide new evidence of associations of epigenetic aging with measures of healthcare access and utilization. If validated, these findings suggest that epigenetic aging biomarkers may be useful in studying disease processes and assessing health outcomes related to access and utilization.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"80"},"PeriodicalIF":4.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076605","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":"Maternal asthma and newborn DNA methylation.","authors":"Casper-Emil Tingskov Pedersen, Thanh T Hoang, Jianping Jin, Anna Starnawska, Raquel Granell, Hannah R Elliott, Anke Huels, Heather J Zar, Dan J Stein, Yining Zhang, Herman T den Dekker, Liesbeth Duijts, Janine F Felix, Júlia Sangüesa, Mariona Bustamante, Maribel Casas, Martine Vrijheid, Latha Kadalayil, Faisal I Rezwan, Hasan Arshad, John W Holloway, Stefan Röder, Ana C Zenclussen, Gunda Herberth, Nicklas Heine Staunstrup, Henriette Thisted Horsdal, Jonathan Mill, Eilis Hannon, Isabella Annesi-Maesano, Giancarlo Pesce, Nour Baïz, Barbara Heude, Sahra Hosseinian-Mohazzab, Carrie V Breton, Sophia Harlid, Justin Harbs, Magnus Domellof, Christina West, Edwina Yeung, Xuehuo Zeng, Wenche Nystad, Siri E Håberg, Maria C Magnus, Diana Schendel, Stephanie J London, Klaus Bønnelykke","doi":"10.1186/s13148-025-01858-4","DOIUrl":"https://doi.org/10.1186/s13148-025-01858-4","url":null,"abstract":"<p><strong>Background: </strong>Prenatal exposure to maternal asthma may influence DNA methylation patterns in offspring, potentially affecting their susceptibility to later diseases including asthma.</p><p><strong>Objective: </strong>To investigate the relationship between parental asthma and newborn blood DNA methylation.</p><p><strong>Methods: </strong>Epigenome-wide association analyses were conducted in 13 cohorts on 7433 newborns with blood methylation data from the Illumina450K or EPIC array. We used fixed effects meta-analyses to identify differentially methylated CpGs (DMCs) and comb-p to identify differentially methylated regions (DMRs) associated with maternal asthma during pregnancy and maternal asthma ever. Paternal asthma was analyzed for comparison. Models were adjusted for covariates and cell-type composition. We examined whether implicated sites related to gene expression analyses in publicly available data for childhood blood and adult lung.</p><p><strong>Results: </strong>We identified 27 CpGs associated with maternal asthma during pregnancy at False Discovery Rate < 0.05 but none for maternal asthma ever. Two distinct CpGs were associated with paternal asthma. We observed 5 DMRs associated with maternal asthma during pregnancy 3 associated with maternal asthma ever and 13 DMRs associated with paternal asthma. Gene expression analysis using data in blood from 832 children and lung from 424 adults showed associations between identified DMCs using maternal asthma and expression of several genes, including HLA genes and HOXA5, previously implicated in asthma or lung function.</p><p><strong>Conclusion: </strong>Parental asthma, especially maternal asthma during pregnancy, may be associated with alterations in newborn DNA methylation. These findings might shed light on underlying mechanisms for asthma susceptibility.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"79"},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962242","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":"Genetic and environmental contributions to epigenetic aging across adolescence and young adulthood.","authors":"Dmitry V Kuznetsov, Yixuan Liu, Alicia M Schowe, Darina Czamara, Jana Instinske, Charlotte K L Pahnke, Markus M Nöthen, Frank M Spinath, Elisabeth B Binder, Martin Diewald, Andreas J Forstner, Christian Kandler, Bastian Mönkediek","doi":"10.1186/s13148-025-01880-6","DOIUrl":"10.1186/s13148-025-01880-6","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic aging estimators commonly track chronological and biological aging, quantifying its accumulation (i.e., epigenetic age acceleration) or speed (i.e., epigenetic aging pace). Their scores reflect a combination of inherent biological programming and the impact of environmental factors, which are suggested to vary at different life stages. The transition from adolescence to adulthood is an important period in this regard, marked by an increasing and, then, stabilizing epigenetic aging variance. Whether this pattern arises from environmental influences or genetic factors is still uncertain. This study delves into understanding the genetic and environmental contributions to variance in epigenetic aging across these developmental stages. Using twin modeling, we analyzed four estimators of epigenetic aging, namely Horvath Acceleration, PedBE Acceleration, GrimAge Acceleration, and DunedinPACE, based on saliva samples collected at two timepoints approximately 2.5 years apart from 976 twins of four birth cohorts (aged about 9.5, 15.5, 21.5, and 27.5 years at first and 12, 18, 24, and 30 years at second measurement occasion).</p><p><strong>Results: </strong>Half to two-thirds (50-68%) of the differences in epigenetic aging were due to unique environmental factors, indicating the role of life experiences and epigenetic drift, besides measurement error. The remaining variance was explained by genetic (Horvath Acceleration: 24%; GrimAge Acceleration: 32%; DunedinPACE: 47%) and shared environmental factors (Horvath Acceleration: 26%; PedBE Acceleration: 47%). The genetic and shared environmental factors represented the primary sources of stable differences in corresponding epigenetic aging estimators over 2.5 years. Age moderation analyses revealed that the variance due to individually unique environmental sources was smaller in younger than in older cohorts in epigenetic aging estimators trained on chronological age (Horvath Acceleration: 47-49%; PedBE Acceleration: 33-68%). The variance due to genetic contributions, in turn, potentially increased across age groups for epigenetic aging estimators trained in adult samples (Horvath Acceleration: 18-39%; GrimAge Acceleration: 24-43%; DunedinPACE: 42-57%).</p><p><strong>Conclusions: </strong>Transition to adulthood is a period of the increasing variance in epigenetic aging. Both environmental and genetic factors contribute to this trend. The degree of environmental and genetic contributions can be partially explained by the design of epigenetic aging estimators.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"78"},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993745","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}