Clinical Epigenetics最新文献

{"title":"Technical and biological sources of unreliability of Infinium probes on Illumina methylation microarrays","authors":"Tatiana Nazarenko, Charlotte Dafni Vavourakis, Allison Jones, Iona Evans, Lena Schreiberhuber, Christine Kastner, Isma Ishaq-Parveen, Elisa Redl, Anthony W. Watson, Kirsten Brandt, Clive Carter, Alexey Zaikin, Chiara Maria Stella Herzog, Martin Widschwendter","doi":"10.1186/s13148-024-01739-2","DOIUrl":"https://doi.org/10.1186/s13148-024-01739-2","url":null,"abstract":"The Illumina Methylation array platform has facilitated countless epigenetic studies on DNA methylation (DNAme) in health and disease, yet relatively few studies have so studied its reliability, i.e., the consistency of repeated measures. Here we investigate the reliability of both type I and type II Infinium probes. We propose a method for excluding unreliable probes based on dynamic thresholds for mean intensity (MI) and ‘unreliability’, estimated by probe-level simulation of the influence of technical noise on methylation β values using the background intensities of negative control probes. We validate our method in several datasets, including newly generated Illumina MethylationEPIC BeadChip v1.0 data from paired whole blood samples taken six weeks apart and technical replicates spanning multiple sample types. Our analysis revealed that specifically probes with low MI exhibit higher β value variability between repeated samples. MI was associated with the number of C-bases in the respective probe sequence and correlated negatively with unreliability scores. The unreliability scores were substantiated through validation in a new EPIC v1.0 (blood and cervix) and a publicly available 450k (blood) dataset, as they effectively captured the variability observed in β values between technical replicates. Finally, despite promising higher robustness, the newer version v2.0 of the MethylationEPIC BeadChip retained a substantial number of probes with poor unreliability scores. To enhance current pre-processing pipelines, we developed an R package to calculate MI and unreliability scores and provide guidance on establishing optimal dynamic score thresholds for a given dataset.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"101 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254177","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":"Methylation alterations of imprinted genes in different placental diseases","authors":"Xuwei Wang, Yunyun Liu, Yuying Wu, Chunxi Lin, Si Yang, Yuhan Yang, Dunjin Chen, Bolan Yu","doi":"10.1186/s13148-024-01738-3","DOIUrl":"https://doi.org/10.1186/s13148-024-01738-3","url":null,"abstract":"Imprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS). In this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2′-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS. This study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"50 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268903","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":"Technical considerations for placental tissue processing and the subsequent impact on genome-wide DNA methylation analysis","authors":"Kristen M. Kocher, Julius Ngwa, Kushal J. Kapse, Surajit Bhattacharya, Christopher Rossi, Emmanuele Delot, Adre duPlessis, Catherine Limperopoulos, Nickie Andescavage","doi":"10.1186/s13148-024-01741-8","DOIUrl":"https://doi.org/10.1186/s13148-024-01741-8","url":null,"abstract":"To assess the impact of postnatal processing on placental DNA methylation, array data from flash-frozen placental tissue was compared to perfluorocarbon-immersed and formalin-fixed paraffin-embedded placental tissue. We observed that tissue exposed to perfluorocarbon showed no significant DNA methylation differences when compared to unprocessed tissue, while formalin processing altered the quality and reliability of the data produced on the DNA methylation array platform. Placental DNA methylation allows for the study of gene–environment interactions that influence the fetal environment and development. Our study highlights that placental post-processing techniques must be considered in the evaluation and interpretation of epigenetic studies.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"6 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268902","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":"Blood-based HYAL2 methylation as a potential marker for the preclinical detection of coronary heart disease and stroke","authors":"Lanfei Bi, Jialie Jin, Yao Fan, Yu Liu, Haifeng Xu, Mengxia Li, Changying Chen, Chong Shen, Rongxi Yang","doi":"10.1186/s13148-024-01742-7","DOIUrl":"https://doi.org/10.1186/s13148-024-01742-7","url":null,"abstract":"Coronary heart disease (CHD) and stroke have become the leading cause of premature mortality and morbidity worldwide. Therefore, sensitive and accurate biomarkers for early detection of CHD and stroke are urgently needed for effective prevention and treatment. We aim to investigate the association between blood-based HYAL2 methylation and the risk of CHD and stroke in Chinese population. In a prospective nested case–control study comprising 171 CHD cases, 139 stroke cases, who developed the diseases after recruitment and 356 controls who remained healthy during the 2.5 years of follow-up time, the methylation level of HYAL2 in the peripheral blood was quantified using mass spectrometry, and the association was calculated by logistic regression adjusted for covariant. Significant association between HYAL2 methylation in the peripheral blood and increased risk of preclinical CHD and stroke were identified [odds ratios (ORs) per − 10% methylation: 1.35–1.64, p ≤ 0.045 for HYAL2_CpG_1, HYAL2_CpG_2 and HYAL2_CpG_3 in CHD; ORs per − 10% methylation: 0.76–1.64, p ≤ 0.033 for HYAL2_CpG_2 and HYAL2_CpG_4 in stroke]. The association in CHD was further enhanced by female gender, younger age (< 70 years old), without the history of hypertension and cancer. The combination of four HYAL2 methylation sites showed an effective discrimination of CHD and stroke cases without hypertension from controls [area under curve (AUC) = 0.78 and 0.75, respectively]. This study presents a strong association of altered HYAL2 methylation in peripheral blood with preclinical CHD and stroke, providing a novel biomarker for risk assessment and early detection of cardiovascular diseases.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"14 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254175","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":"Correction: A systematic review on the contribution of DNA methylation to hearing loss","authors":"Vibha Patil, Patricia Perez-Carpena, Jose A. Lopez-Escamez","doi":"10.1186/s13148-024-01733-8","DOIUrl":"https://doi.org/10.1186/s13148-024-01733-8","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Clinical Epigenetics (2024) 16:88&lt;/b&gt; &lt;b&gt;https://doi.org/10.1186/s13148-024-01697-9&lt;/b&gt;&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Following publication of the original article [1], the authors noticed the error in Fig. 1. The typesetter has inadvertently processed the flowchart with a missing box in the figure. The correct Fig. 1 has been presented with this erratum.&lt;/p&gt;&lt;figure&gt;&lt;figcaption&gt;&lt;b data-test=\"figure-caption-text\"&gt;Fig. 1&lt;/b&gt;&lt;/figcaption&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13148-024-01733-8/MediaObjects/13148_2024_1733_Fig1_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"805\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13148-024-01733-8/MediaObjects/13148_2024_1733_Fig1_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;p&gt;Flow diagram for the DNA methylation study selection&lt;/p&gt;&lt;span&gt;Full size image&lt;/span&gt;&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/figure&gt;&lt;p&gt;The original article has been corrected.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Patil V, Perez-Carpena P, Lopez-Escamez JA. A systematic review on the contribution of DNA methylation to hearing loss. Clin Epigenet. 2024;16:88.&lt;/p&gt;&lt;p&gt;Article CAS Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Meniere’s Disease Neuroscience Research Program, Faculty of Medicine and Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Rm 611024, Level 11 Kolling Institute | 10 Westbourne St, St Leonards, Sydney, NSW, 2064, Australia&lt;/p&gt;&lt;p&gt;Vibha Patil &amp; Jose A. Lopez-Escamez&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Division of Otolaryngology, Department of Surgery, Instituto de Investigación Biosanitaria, Ibs.Granada, Universidad de Granada, Granada, Spain&lt;/p&gt;&lt;p&gt;Patricia Perez-Carpena &amp; Jose A. Lopez-Escamez&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Otology &amp; Neurotology Group CTS495, Instituto de Investigación Biosanitaria, Ibs.GRANADA, Universidad de Granada, Granada, Spain&lt;/p&gt;&lt;p&gt;Patricia Perez-Carpena &amp; Jose A. Lopez-Escamez&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Sensorineural Pathology Program, Centro de Investigación Biomédica en Red en Enfermedades Raras, CIBERER, Madrid, Spain&lt;/p&gt;&lt;p&gt;Patricia Perez-Carpena &amp; Jose A. Lopez-Escamez&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Otolaryngology, Hospital Universitario San Cecilio, Instituto de Investigacion Biosanitaria, Ibs.GRANADA, Granada, Spain&lt;/p&gt;&lt;p&gt;Patricia Perez-Carpena&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Vibha Patil&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/s","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"10 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254176","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":"N6-methyladenosine (m6A) RNA modification in fibrosis and collagen-related diseases","authors":"Man Tan, Siyi Liu, Lubin Liu","doi":"10.1186/s13148-024-01736-5","DOIUrl":"https://doi.org/10.1186/s13148-024-01736-5","url":null,"abstract":"Fibrosis is an abnormal tissue healing process characterized by the excessive accumulation of ECM components, such as COL I and COL III, in response to tissue injury or chronic inflammation. Recent advances in epitranscriptomics have underscored the importance of m6A modification in fibrosis. m6A, the most prevalent modification in eukaryotic RNA, is catalyzed by methyltransferases (e.g., METTL3), removed by demethylases (e.g., FTO), and recognized by reader proteins (e.g., YTHDF1/2). These modifications are crucial in regulating collagen metabolism and associated diseases. Understanding the role of m6A modification in fibrosis and other collagen-related conditions holds promise for developing targeted therapies. This review highlights the latest progress in this area.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"20 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223417","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":"Continued decitabine/all-trans retinoic acid treatment: extended complete remission in an elderly AML patient with multi-hit TP53 lesions and complex-monosomal karyotype","authors":"Johanna Thomas, Usama-Ur Rehman, Helena Bresser, Olga Grishina, Dietmar Pfeifer, Etienne Sollier, Konstanze Döhner, Christoph Plass, Heiko Becker, Claudia Schmoor, Maike de Wit, Michael Lübbert","doi":"10.1186/s13148-024-01737-4","DOIUrl":"https://doi.org/10.1186/s13148-024-01737-4","url":null,"abstract":"DNA-hypomethylating agents (HMAs) induce notable remission rates in AML/MDS patients with TP53 mutations; however, secondary resistance often develops rapidly. In the DECIDER trial (NCT00867672), elderly AML patients (also those with adverse genetics) randomized to all-trans retinoic acid (ATRA) added to decitabine (DEC) attained significantly delayed time-to-resistance. An 82-year-old patient with a non-disruptive, in-frame TP53 mutation (p.Cys238_Asn239delinsTyr, VAF 90%) and complex-monosomal karyotype attained a complete hematologic and cytogenetic remission with DEC + ATRA, with 3.7 years survival after 30 treatment cycles that were well-tolerated. Further HMA + ATRA studies appear warranted in AML/MDS patients of different genetic risk groups ineligible for more intensive treatment. Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT00867672","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"62 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223416","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":"Genome-wide characterization of dynamic DNA 5-hydroxymethylcytosine and TET2-related DNA demethylation during breast tumorigenesis","authors":"Shuang-Ling Wu, Lin Yang, Changcai Huang, Qing Li, Chunhui Ma, Fang Yuan, Yinglin Zhou, Xiaoyue Wang, Wei-Min Tong, Yamei Niu, Feng Jin","doi":"10.1186/s13148-024-01726-7","DOIUrl":"https://doi.org/10.1186/s13148-024-01726-7","url":null,"abstract":"Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous. DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA). Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"133 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178259","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":"Epigenetics and immunotherapy in colorectal cancer: progress and promise","authors":"Tianjiao Dang, Xin Guan, Luying Cui, Yuli Ruan, Zhuo Chen, Haoyi Zou, Ya Lan, Chao Liu, Yanqiao Zhang","doi":"10.1186/s13148-024-01740-9","DOIUrl":"https://doi.org/10.1186/s13148-024-01740-9","url":null,"abstract":"Colorectal cancer (CRC) is a common malignant tumor with the third and second highest incidence and mortality rates among various malignant tumors. Despite significant advancements in the present therapy for CRC, the majority of CRC cases feature proficient mismatch repair/microsatellite stability and have no response to immunotherapy. Therefore, the search for new treatment options holds immense importance in the diagnosis and treatment of CRC. In recent years, clinical research on immunotherapy combined with epigenetic therapy has gradually increased, which may bring hope for these patients. This review explores the role of epigenetic regulation in exerting antitumor effects through its action on immune cell function and highlights the potential of certain epigenetic genes that can be used as markers of immunotherapy to predict therapeutic efficacy. We also discuss the application of epigenetic drug sensitization immunotherapy to develop new treatment options combining epigenetic therapy and immunotherapy.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"5 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178260","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":"DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain","authors":"Danni A. Gadd, Hannah M. Smith, Donncha Mullin, Ola Chybowska, Robert F. Hillary, Dorien M. Kimenai, Elena Bernabeu, Yipeng Cheng, Chloe Fawns-Ritchie, Archie Campbell, Danielle Page, Adele Taylor, Janie Corley, Maria Del C. Valdés-Hernández, Susana Muñoz Maniega, Mark E. Bastin, Joanna M. Wardlaw, Rosie M. Walker, Kathryn L. Evans, Andrew M. McIntosh, Caroline Hayward, Tom C. Russ, Sarah E. Harris, Paul Welsh, Naveed Sattar, Simon R. Cox, Daniel L. McCartney, Riccardo E. Marioni","doi":"10.1186/s13148-024-01734-7","DOIUrl":"https://doi.org/10.1186/s13148-024-01734-7","url":null,"abstract":"Plasma growth differentiation factor 15 (GDF15) and N‐terminal proB‐type natriuretic peptide (NT‐proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification. In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36–1.41, PFDR < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7–12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population. EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"44 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}