Clinical Epigenetics最新文献

{"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}

{"title":"Influence of race, ethnicity, and sex on the performance of epigenetic predictors of phenotypic traits.","authors":"Dennis Khodasevich, Nicole Gladish, Saher Daredia, Anne K Bozack, Hanyang Shen, Jamaji C Nwanaji-Enwerem, Belinda L Needham, David H Rehkopf, Andres Cardenas","doi":"10.1186/s13148-025-01864-6","DOIUrl":"https://doi.org/10.1186/s13148-025-01864-6","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation-based predictors of phenotypic traits including leukocyte proportions, smoking activity, biological aging, and circulating levels of plasma proteins are widely used as biomarkers in public health research. However, limited racial and ethnic diversity of research participants is an ongoing issue for epigenetics research, and the potential downstream impacts of limited diversity in training samples on the performance of epigenetic predictors remains poorly understood. We examined the performance of epigenetic predictors of chronological age (also known as epigenetic clocks), telomere length, cell proportions, and plasma proteins within a diverse sample of adult NHANES participants during the 1999-2000 and 2001-2002 survey cycles, both overall and stratified by self-reported race/ethnicity and sex. We utilized correlation coefficients and median absolute errors (MAE) to judge predictor performance, and bootstrapping and multivariate regression to assess the significance of differences between groups.</p><p><strong>Results: </strong>All epigenetic predictors were significantly associated with their corresponding phenotypic traits in the overall population, with particularly high correlations for the epigenetic clocks and cell proportion estimates. Several significant differences in performance were observed between racial/ethnic groups, particularly for the plasma protein predictors, with a reoccurring trend of lower correlation in Mexican American and non-Hispanic Black participants compared to non-Hispanic White participants. Sex-differences in performance for several predictors were also identified but were not as pronounced. Multivariate regression models indicated that disparities in epigenetic predictor performance persisted after accounting for overall differences in epigenetic predictions related to race/ethnicity and sex, as well as further adjustment for estimated cell proportions and SES variables.</p><p><strong>Conclusions: </strong>We found evidence for substantial disparities in epigenetic predictor performance, with each predictor exhibiting at least one significant difference in correlation or MAE related to race, ethnicity, or sex.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"59"},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968277","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":"Cross-sectional and longitudinal association of seven DNAm-based predictors with metabolic syndrome and type 2 diabetes.","authors":"Suet Mei Chew, Alexander Teumer, Pamela R Matías-García, Christian Gieger, Juliane Winckelmann, Karsten Suhre, Christian Herder, Wolfgang Rathmann, Annette Peters, Melanie Waldenberger","doi":"10.1186/s13148-025-01862-8","DOIUrl":"10.1186/s13148-025-01862-8","url":null,"abstract":"<p><strong>Background: </strong>To date, various epigenetic clocks have been constructed to estimate biological age, most commonly using DNA methylation (DNAm). These include \"first-generation\" clocks such as DNAmAgeHorvath and \"second-generation\" clocks such as DNAmPhenoAge and DNAmGrimAge. The divergence of one's predicted DNAm age from chronological age, termed DNAmAge acceleration (AA), has been linked to mortality and various aging-related conditions, albeit with varying findings. In metabolic syndrome (MetS) and type 2 diabetes (T2D), it remains inconclusive which DNAm-based predictor(s) is/are closely related to these two metabolic conditions. Therefore, we examined the cross-sectional associations between seven DNAm-based predictors and prevalent metabolic conditions in participants with methylation data from the KORA study. We also analyzed the longitudinal association with time-to-incident T2D and the relative prognostic value compared to clinical predictors from the Framingham 8-year T2D risk function in predicting incident disease over eight years.</p><p><strong>Results: </strong>GrimAA and PhenoAA difference demonstrated consistently significant associations in the cross-sectional and longitudinal analyses. GrimAA difference reported a larger effect: with prevalent MetS at F4 (odds ratio = 1.09, 95% confidence interval = [1.06-1.13], p = 2.04E-08), with prevalent T2D at F4 (odds ratio = 1.09 [1.04-1.13], p = 1.38E-04) and with time-to-incident T2D (hazards ratio = 1.05 [1.01-1.10], p = 0.02) for each year increase in GrimAA difference. Mortality risk score was significantly associated with both prevalent metabolic conditions but not in the longitudinal analysis. The inclusion of DNAm-based predictor in the model with Framingham clinical predictors improved discriminative ability, albeit not significantly. Notably, the DNAm-based predictor, when fitted separately, showed a discriminative ability comparable to that of the model with clinical predictors. Overall, no clear pattern of significant associations was identified in the epigenetic measures from the \"first-generation\" clocks.</p><p><strong>Conclusions: </strong>GrimAA, PhenoAA difference and mortality risk score, derived from the \"second-generation\" clocks, demonstrated significant associations with both MetS and T2D. These DNAm-based predictors may be useful biomarkers for risk stratification and disease prognosis in our study sample of European ancestry. Further research is warranted to investigate the generalizability of our findings across different ancestries and to examine the underlying shared biological mechanisms.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"58"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810715","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":"Targeting the epigenetic regulation of ferroptosis: a potential therapeutic approach for sepsis-associated acute kidney injury.","authors":"Yuhang Yang, Xinqi Deng, Wenyuan Li, Yan Leng, Yonghong Xiong, Bihan Wang, Siyuan Gong, Yunhao Wang, Baichuan Yang, Wei Li","doi":"10.1186/s13148-025-01861-9","DOIUrl":"10.1186/s13148-025-01861-9","url":null,"abstract":"<p><p>Sepsis is a syndrome of organ dysfunction caused by the invasion of pathogenic microorganisms. In clinical practice, patients with sepsis are prone to concurrent acute kidney injury, which has high morbidity and mortality rates. Thus, understanding the pathogenesis of sepsis-associated acute kidney injury is of significant clinical importance. Ferroptosis is an iron-dependent programmed cell death pathway, which is proved to play a critical role in the process of sepsis-associated acute kidney injury through various mechanisms. Epigenetic regulation modulates the content and function of nucleic acids and proteins within cells through various modifications. Its impact on ferroptosis has garnered increasing attention; however, the role of epigenetic regulation targeting ferroptosis in sepsis-associated acute kidney injury has not been fully elucidated. Growing evidence suggests that epigenetic regulation can modulate ferroptosis through complex pathway networks, thereby affecting the development and prognosis of sepsis-associated acute kidney injury. This paper summarizes the impact of ferroptosis on sepsis-associated acute kidney injury and the regulatory mechanisms of epigenetic regulation on ferroptosis, providing new insights for the targeted therapy of sepsis-associated acute kidney injury.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"57"},"PeriodicalIF":4.8,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794732","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":"Comparative performance evaluation of bisulfite- and enzyme-based DNA conversion methods.","authors":"Roy B Simons, Faidra Karkala, Marta M Kukk, Hieab H H Adams, Manfred Kayser, Athina Vidaki","doi":"10.1186/s13148-025-01855-7","DOIUrl":"10.1186/s13148-025-01855-7","url":null,"abstract":"<p><strong>Background: </strong>Bisulfite conversion (BC) has been the gold standard in DNA methylation profiling for decades. During this chemical process, non-methylated cytosines are converted into uracils, while methylated cytosines remain intact. Despite its popularity, BC has major drawbacks when used for sensitive applications with low-quality and -quantity DNA samples, such as the required large amount of DNA input, the caused DNA fragmentation and loss, and the resulting reduced sequence complexity. Lately, to account for BC-related disadvantages the first commercial enzymatic conversion (EC) kit was launched. While EC follows the same conversion principle as BC it uses two enzymatic steps instead of one chemical step with BC. In this study, we validated and compared the conversion performance of the most widely used BC and EC kits using a multiplex qPCR assay (qBiCo) we recently developed, which provides several indexes: conversion efficiency, converted DNA recovery and fragmentation.</p><p><strong>Results: </strong>Firstly, we implemented and standardized both DNA conversion methods. Secondly, using qBiCo, we performed a developmental validation for both conversion approaches, including testing the following parameters: repeatability, reproducibility, sensitivity and robustness. Regarding conversion efficiency, both methods performed similarly, with the limit of reproducible conversion being 5 ng and 10 ng for BC and EC, respectively. The recovery, however, is structurally overestimated for BC: 2.3 ± 0.7 and 0.7 ± 0.2 for EC. In contrast, degraded DNA input resulted in high fragmentation values after BC and low-medium values for EC (14.4 ± 1.2 and 3.3 ± 0.4, respectively). Finally, we converted 10 ng of 22 genomic DNA samples using both methods. We observed an overestimation of the BC DNA recovery (130%) and a low recovery for EC (40%).</p><p><strong>Conclusions: </strong>Our findings indicate that both DNA conversion methods have strengths and weaknesses. BC shows a high recovery, whereas EC does not cause extensive fragmentation that is characteristic to BC. EC is, therefore, more robust to the analysis of degraded DNA such as forensic-type or cell-free DNA, at least for the genomic DNA inputs tested here. We believe that the low recovery of EC could be improved by further optimizing and automating the bead-based cleanup steps. Overall, our study provides the first independent benchmarking of bisulfite- and enzyme-based conversion kits.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"56"},"PeriodicalIF":4.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779280","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":"Sleep disturbances, shift work, and epigenetic ageing in working-age adults: findings from the Young Finns study.","authors":"Ida Autio, Aino Saarinen, Saara Marttila, Emma Raitoharju, Pashupati P Mishra, Nina Mononen, Mika Kähönen, Liisa Keltikangas-Järvinen, Olli Raitakari, Terho Lehtimäki","doi":"10.1186/s13148-025-01860-w","DOIUrl":"10.1186/s13148-025-01860-w","url":null,"abstract":"<p><strong>Background: </strong>Sleep disturbances are known to have adverse effects on health, but knowledge on the effect of sleep disturbances on epigenetic ageing is limited. We investigated (1) whether symptoms of insomnia, obstructive sleep apnoea, sleep deprivation, and circadian rhythm lateness are associated with epigenetic ageing, and (2) whether years spent in shift work moderates these associations.</p><p><strong>Methods: </strong>We used the population-based Young Finns data (n = 1618). Epigenetic clocks such as AgeDev_Hannum, AgeDev_Horvath, AgeDev_Pheno, AgeDev_Grim, and DunedinPACE were utilized to measure epigenetic ageing. Sleep was evaluated using various validated self-report questionnaires. Covariates included sex, array type, smoking status, health behaviours, socioeconomic factors, and cardiovascular health factors.</p><p><strong>Results: </strong>Among the various sleep measures, obstructive sleep apnoea symptoms were most consistently linked to accelerated epigenetic ageing, as measured by AgeDev_Grim and DunedinPACE. Insomnia, sleep deprivation, and years spent in shift work were not associated with epigenetic ageing after adjusting for health-related or socioeconomic covariates. Additionally, we found interactions between years spent in shift work and sleep disturbances when accounting for epigenetic ageing. Among those with little to no history of shift work, both insomnia and sleep deprivation were associated with more accelerated epigenetic ageing in AgeDev_Grim when compared to long-term shift workers. However, the pace of epigenetic ageing (measured with DunedinPACE) appears to be higher in those with both sleep deprivation and longer history of shift work.</p><p><strong>Conclusions: </strong>Among various sleep measures, symptoms of obstructive sleep apnoea appear to be most consistently associated with accelerated epigenetic ageing even after adjusting for various health-related and socioeconomic factors. Shift work seems to have a crucial role in the relationship between sleep disturbances and epigenetic ageing in working-age adults.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"55"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771411","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":"Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.","authors":"Yao Hu, Jeff Haessler, Jessica I Lundin, Burcu F Darst, Eric A Whitsel, Megan Grove, Weihua Guan, Rui Xia, Mindy Szeto, Laura M Raffield, Scott Ratliff, Yuxuan Wang, Xuzhi Wang, Alison E Fohner, Megan T Lynch, Yesha M Patel, S Lani Park, Huichun Xu, Braxton D Mitchell, Joshua C Bis, Nona Sotoodehnia, Jennifer A Brody, Bruce M Psaty, Gina M Peloso, Michael Y Tsai, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Sharon L R Kardia, Alex P Reiner, Leslie Lange, Myriam Fornage, James S Pankow, Mariaelisa Graff, Kari E North, Charles Kooperberg, Ulrike Peters","doi":"10.1186/s13148-025-01859-3","DOIUrl":"10.1186/s13148-025-01859-3","url":null,"abstract":"<p><p>Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations. In addition, knowledge of nongenetic factors on lipid profiles is extremely limited. In the Population Architecture Using Genomics and Epidemiology (PAGE) Study, we performed methylome-wide association analysis on 9,561 participants from diverse race and ethnicity backgrounds for HDL-c, LDL-c, TC, and TG levels, and also tested interactions between smoking or alcohol intake and methylation in their association with lipid levels. We identified novel CpG sites at 16 loci (P < 1.18E-7) with successful replication on 3,215 participants. One additional novel locus was identified in the self-reported White participants (P = 4.66E-8). Although no additional CpG sites were identified in the genome-wide interaction analysis, 13 reported CpG sites showed significant heterogeneous association across smoking or alcohol intake strata. By mapping novel and reported CpG sites to genes, we identified enriched pathways directly linked to lipid metabolism as well as ones spanning various biological functions. These findings provide new insights into the regulation of lipid concentrations.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"54"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771408","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":"Correction: Respiratory infection‑ and asthma‑prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways.","authors":"David Martino, Nikki Schultz, Ravinder Kaur, Simon D van Haren, Nina Kresoje, Annmarie Hoch, Joann Diray-Arce, Jessica Lasky Su, Ofer Levy, Michael Pichichero","doi":"10.1186/s13148-025-01848-6","DOIUrl":"https://doi.org/10.1186/s13148-025-01848-6","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"53"},"PeriodicalIF":4.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742479","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}