Epigenetics最新文献_第7页

Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations in CD46 and other loci. 老年人脑组织表观遗传皮层时钟年龄的遗传结构：CD46 和其他位点的改变。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-08-22 DOI: 10.1080/15592294.2024.2392050

Francine Grodstein, Bernardo Lemos, Jingyun Yang, Katia de Paiva Lopes, Ricardo A Vialle, Nicholas Seyfried, Yanling Wang, Gemma Shireby, Eilis Hannon, Alan Thomas, Keeley Brookes, Jonathan Mill, Philip L De Jager, David A Bennett

{"title":"Genetic architecture of epigenetic cortical clock age in brain tissue from older individuals: alterations in CD46 and other loci.","authors":"Francine Grodstein, Bernardo Lemos, Jingyun Yang, Katia de Paiva Lopes, Ricardo A Vialle, Nicholas Seyfried, Yanling Wang, Gemma Shireby, Eilis Hannon, Alan Thomas, Keeley Brookes, Jonathan Mill, Philip L De Jager, David A Bennett","doi":"10.1080/15592294.2024.2392050","DOIUrl":"10.1080/15592294.2024.2392050","url":null,"abstract":"The cortical epigenetic clock was developed in brain tissue as a biomarker of brain aging. As one way to identify mechanisms underlying aging, we conducted a GWAS of cortical age. We leveraged postmortem cortex tissue and genotyping array data from 694 participants of the Rush Memory and Aging Project and Religious Orders Study (ROSMAP; 11000,000 SNPs), and meta-analysed ROSMAP with 522 participants of Brains for Dementia Research (5,000,000 overlapping SNPs). We confirmed results using eQTL (cortical bulk and single nucleus gene expression), cortical protein levels (ROSMAP), and phenome-wide association studies (clinical/neuropathologic phenotypes, ROSMAP). In the meta-analysis, the strongest association was rs4244620 (p = 1.29 × 10-7), which also exhibited FDR-significant cis-eQTL effects for CD46 in bulk and single nucleus (microglia, astrocyte, oligodendrocyte, neuron) cortical gene expression. Additionally, rs4244620 was nominally associated with lower cognition, faster slopes of cognitive decline, and greater Parkinsonian signs (n ~ 1700 ROSMAP with SNP/phenotypic data; all p ≤ 0.04). In ROSMAP alone, the top SNP was rs4721030 (p = 8.64 × 10-8) annotated to TMEM106B and THSD7A. Further, in ROSMAP (n = 849), TMEM106B and THSD7A protein levels in cortex were related to many phenotypes, including greater AD pathology and lower cognition (all p ≤ 0.0007). Overall, we identified converging evidence of CD46 and possibly TMEM106B/THSD7A for potential roles in cortical epigenetic clock age.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2392050"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016751","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}

引用次数: 0

Circ-0006332 stimulates cardiomyocyte pyroptosis via the miR-143/TLR2 axis to promote doxorubicin-induced cardiac damage. Circ-0006332通过miR-143/TLR2轴刺激心肌细胞热解，促进多柔比星诱导的心脏损伤。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-07-17 DOI: 10.1080/15592294.2024.2380145

Ping Zhang, Yuanyuan Liu, Yuliang Zhan, Pengtao Zou, Xinyong Cai, Yanmei Chen, Liang Shao

{"title":"Circ-0006332 stimulates cardiomyocyte pyroptosis via the miR-143/TLR2 axis to promote doxorubicin-induced cardiac damage.","authors":"Ping Zhang, Yuanyuan Liu, Yuliang Zhan, Pengtao Zou, Xinyong Cai, Yanmei Chen, Liang Shao","doi":"10.1080/15592294.2024.2380145","DOIUrl":"10.1080/15592294.2024.2380145","url":null,"abstract":"Doxorubicin (DOX)-mediated cardiotoxicity can impair the clinical efficacy of chemotherapy, leading to heart failure (HF). Given the importance of circRNAs and miRNAs in HF, this paper intended to delineate the mechanism of the circular RNA 0006332 (circ -0,006,332)/microRNA (miR)-143/Toll-like receptor 2 (TLR2) axis in doxorubicin (DOX)-induced HF. The binding of miR-143 to circ -0,006,332 and TLR2 was assessed with the dual-luciferase assay, and the binding between miR-143 and circ -0,006,332 was determined with FISH, RIP, and RNA pull-down assays. miR-143 and/or circ -0,006,332 were overexpressed in rats and cardiomyocytes, followed by DOX treatment. In cardiomyocytes, miR-143 and TLR2 expression, cell viability, LDH release, ATP contents, and levels of IL-1β, IL-18, TNF-α, and pyroptosis-related molecules were examined. In rats, cardiac function, serum levels of cardiac enzymes, apoptosis, myocardial fibrosis, and levels of IL-1β, IL-18, TNF-α, TLR2, and pyroptosis-related molecules were detected. miR-143 diminished TLR2 expression by binding to TLR2, and circ -0,006,332 bound to miR-143 to downregulate miR-143 expression. miR-143 expression was reduced and TLR2 expression was augmented in DOX-induced cardiomyocytes. miR-143 inhibited DOX-induced cytotoxicity by suppressing pyroptosis in H9C2 cardiomyocytes. In DOX-induced rats, miR-143 reduced cardiac dysfunction, myocardial apoptosis, myocardial fibrosis, TLR2 levels, and pyroptosis. Furthermore, overexpression of circ -0,006,332 blocked these effects of miR-143 on DOX-induced cardiomyocytes and rats. Circ -0,006,332 stimulates cardiomyocyte pyroptosis by downregulating miR-143 and upregulating TLR2, thus promoting DOX-induced cardiac injury.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2380145"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632973","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}

引用次数: 0

Novel DNA methylation changes in mouse lungs associated with chronic smoking. 与长期吸烟有关的小鼠肺部 DNA 甲基化新变化

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-03-04 DOI: 10.1080/15592294.2024.2322386

Chinonye Doris Onuzulu, Samantha Lee, Sujata Basu, Jeannette Comte, Yan Hai, Nikho Hizon, Shivam Chadha, Maria Shenna Fauni, Andrew J Halayko, Christopher D Pascoe, Meaghan J Jones

{"title":"Novel DNA methylation changes in mouse lungs associated with chronic smoking.","authors":"Chinonye Doris Onuzulu, Samantha Lee, Sujata Basu, Jeannette Comte, Yan Hai, Nikho Hizon, Shivam Chadha, Maria Shenna Fauni, Andrew J Halayko, Christopher D Pascoe, Meaghan J Jones","doi":"10.1080/15592294.2024.2322386","DOIUrl":"10.1080/15592294.2024.2322386","url":null,"abstract":"Smoking is a potent cause of asthma exacerbations, chronic obstructive pulmonary disease (COPD) and many other health defects, and changes in DNA methylation (DNAm) have been identified as a potential link between smoking and these health outcomes. However, most studies of smoking and DNAm have been done using blood and other easily accessible tissues in humans, while evidence from more directly affected tissues such as the lungs is lacking. Here, we identified DNAm patterns in the lungs that are altered by smoking. We used an established mouse model to measure the effects of chronic smoke exposure first on lung phenotype immediately after smoking and then after a period of smoking cessation. Next, we determined whether our mouse model recapitulates previous DNAm patterns observed in smoking humans, specifically measuring DNAm at a candidate gene responsive to cigarette smoke, Cyp1a1. Finally, we carried out epigenome-wide DNAm analyses using the newly released Illumina mouse methylation microarrays. Our results recapitulate some of the phenotypes and DNAm patterns observed in human studies but reveal 32 differentially methylated genes specific to the lungs which have not been previously associated with smoking. The affected genes are associated with nicotine dependency, tumorigenesis and metastasis, immune cell dysfunction, lung function decline, and COPD. This research emphasizes the need to study CS-mediated DNAm signatures in directly affected tissues like the lungs, to fully understand mechanisms underlying CS-mediated health outcomes.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2322386"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021232","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}

引用次数: 0

Epigenetic changes in pyloric caeca of Atlantic salmon fed diets containing increasing levels of lipids and choline. 大西洋鲑幽门盲肠的表观遗传学变化，喂食含脂量和胆碱量不断增加的食物。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-01-28 DOI: 10.1080/15592294.2024.2305079

Anusha K S Dhanasiri, Daphne Siciliani, Trond M Kortner, Åshild Krogdahl

{"title":"Epigenetic changes in pyloric caeca of Atlantic salmon fed diets containing increasing levels of lipids and choline.","authors":"Anusha K S Dhanasiri, Daphne Siciliani, Trond M Kortner, Åshild Krogdahl","doi":"10.1080/15592294.2024.2305079","DOIUrl":"10.1080/15592294.2024.2305079","url":null,"abstract":"An earlier study of ours investigating the effect of dietary lipid levels on the choline requirement of Atlantic salmon showed increasing severity of intestinal steatosis with increasing lipid levels. As choline is involved in epigenetic regulation by being the key methyl donor, pyloric caeca samples from the study were analysed for epigenetic effects of dietary lipid and choline levels. The diets varied in lipid levels between 16% and 28%, and choline levels between 1.9 and 2.3 g/kg. The diets were fed for 8 weeks to Atlantic salmon of 25 g of initial weight. Using reduced representation bisulfite sequencing (RRBS), this study revealed that increasing dietary lipid levels induced methylation differences in genes involved in membrane transport and signalling pathways, and in microRNAs important for the regulation of lipid homoeostasis. Increasing choline levels also affected genes involved in fatty acid biosynthesis and transport, lipolysis, and lipogenesis, as well as important immune genes. Our observations confirmed that choline is involved in epigenetic regulation in Atlantic salmon, as has been reported for higher vertebrates. This study showed the need for the inclusion of biomarkers of epigenetic processes in studies that must be conducted to define optimal choline levels in diets for Atlantic salmon.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2305079"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569951","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}

引用次数: 0

The one-carbon metabolism as an underlying pathway for placental DNA methylation - a systematic review. 作为胎盘 DNA 甲基化潜在途径的一碳代谢--系统综述。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-03-14 DOI: 10.1080/15592294.2024.2318516

Marjolein M van Vliet, Sam Schoenmakers, Joost Gribnau, Régine P M Steegers-Theunissen

{"title":"The one-carbon metabolism as an underlying pathway for placental DNA methylation - a systematic review.","authors":"Marjolein M van Vliet, Sam Schoenmakers, Joost Gribnau, Régine P M Steegers-Theunissen","doi":"10.1080/15592294.2024.2318516","DOIUrl":"10.1080/15592294.2024.2318516","url":null,"abstract":"Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B12 provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 (n = 15) and in vitro studies (n = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation (n = 9), (2) genome-wide analyses (n = 4), and (3) gene specific (n = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including LEP, NR3C1, CRH, and PlGF; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2318516"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131045","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}

引用次数: 0

Dynamics of DNA methylation during osteogenic differentiation of porcine synovial membrane mesenchymal stem cells from two metabolically distinct breeds. 来自两个代谢不同品种的猪滑膜间充质干细胞成骨分化过程中 DNA 甲基化的动态变化。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-07-02 DOI: 10.1080/15592294.2024.2375011

Shuaichen Li, Puntita Siengdee, Frieder Hadlich, Nares Trakooljul, Michael Oster, Henry Reyer, Klaus Wimmers, Siriluck Ponsuksili

{"title":"Dynamics of DNA methylation during osteogenic differentiation of porcine synovial membrane mesenchymal stem cells from two metabolically distinct breeds.","authors":"Shuaichen Li, Puntita Siengdee, Frieder Hadlich, Nares Trakooljul, Michael Oster, Henry Reyer, Klaus Wimmers, Siriluck Ponsuksili","doi":"10.1080/15592294.2024.2375011","DOIUrl":"10.1080/15592294.2024.2375011","url":null,"abstract":"Mesenchymal stem cells (MSCs), with the ability to differentiate into osteoblasts, adipocytes, or chondrocytes, show evidence that the donor cell's metabolic type influences the osteogenic process. Limited knowledge exists on DNA methylation changes during osteogenic differentiation and the impact of diverse donor genetic backgrounds on MSC differentiation. In this study, synovial membrane mesenchymal stem cells (SMSCs) from two pig breeds (Angeln Saddleback, AS; German Landrace, DL) with distinct metabolic phenotypes were isolated, and the methylation pattern of SMSCs during osteogenic induction was investigated. Results showed that most differentially methylated regions (DMRs) were hypomethylated in osteogenic-induced SMSC group. These DMRs were enriched with genes of different osteogenic signalling pathways at different time points including Wnt, ECM, TGFB and BMP signalling pathways. AS pigs consistently exhibited a higher number of hypermethylated DMRs than DL pigs, particularly during the peak of osteogenesis (day 21). Predicting transcription factor motifs in regions of DMRs linked to osteogenic processes and donor breeds revealed influential motifs, including KLF1, NFATC3, ZNF148, ASCL1, FOXI1, and KLF5. These findings contribute to understanding the pattern of methylation changes promoting osteogenic differentiation, emphasizing the substantial role of donor the metabolic type and epigenetic memory of different donors on SMSC differentiation.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2375011"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491359","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}

引用次数: 0

Combined exercise training decreases blood pressure in OLDER women with NOS3 polymorphism providing changes in differentially methylated regions (DMRs). 联合运动训练可降低患有 NOS3 多态性的老年妇女的血压，并提供不同甲基化区域（DMRs）的变化。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-07-05 DOI: 10.1080/15592294.2024.2375030

Guilherme da Silva Rodrigues, Natalia Yumi Noronha, João Gabriel Ribeiro de Lima, Isabela Harumi Yonehara Noma, Andressa Crystine da Silva Sobrinho, Luísa Maria Diani, Ana P Pinto, Karine Pereira Rodrigues, Marcela Augusta de Souza Pinhel, Carla Barbosa Nonino, Lígia Moriguchi Watanabe, Carlos Roberto Bueno Júnior

{"title":"Combined exercise training decreases blood pressure in OLDER women with NOS3 polymorphism providing changes in differentially methylated regions (DMRs).","authors":"Guilherme da Silva Rodrigues, Natalia Yumi Noronha, João Gabriel Ribeiro de Lima, Isabela Harumi Yonehara Noma, Andressa Crystine da Silva Sobrinho, Luísa Maria Diani, Ana P Pinto, Karine Pereira Rodrigues, Marcela Augusta de Souza Pinhel, Carla Barbosa Nonino, Lígia Moriguchi Watanabe, Carlos Roberto Bueno Júnior","doi":"10.1080/15592294.2024.2375030","DOIUrl":"10.1080/15592294.2024.2375030","url":null,"abstract":"The mechanisms by which the ageing process is associated to an unhealthy lifestyle and how they play an essential role in the aetiology of systemic arterial hypertension have not yet been completely elucidated. Our objective is to investigate the influence of NOS3 polymorphisms [-786T > C and (Glu298Asp)] on systolic blood pressure (SBP) and diastolic blood pressure (DBP) response, differentially methylated regions (DMRs), and physical fitness of adult and older women after a 14-week combined training intervention. The combined training was carried out for 14 weeks, performed 3 times a week, totalling 180 minutes weekly. The genotyping experiment used Illumina Infinium Global Screening Array version 2.0 (GSA V2.0) and Illumina's EPIC Infinium Methylation BeadChip. The participants were separated into SNP rs2070744 in TT (59.7 ± 6.2 years) and TC + CC (60.0 ± 5.2 years), and SNP rs17999 in GluGlu (58.8 ± 5.7 years) and GluAsp + AspAsp (61.6 ± 4.9 years). We observed an effect of time for variables BP, physical capacities, and cholesterol. DMRs related to SBP and DBP were identified for the rs2070744 and rs17999 groups pre- and decreased numbers of DMRs post-training. When we analysed the effect of exercise training in pre- and post-comparisons, the GluGlu SNP (rs17999) showed 10 DMRs, and after enrichment, we identified several biological biases. The combined training improved the SBP and DBP values of the participants regardless of the SNPs. In addition, exercise training affected DNA methylation differently between the groups of NOS3 polymorphisms.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2375030"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534027","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}

引用次数: 0

Parental arsenic exposure and tissue-specific DNA methylation in Bangladeshi infants with spina bifida. 孟加拉脊柱裂婴儿的父母砷暴露和组织特异性 DNA 甲基化。

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-10-19 DOI: 10.1080/15592294.2024.2416345

Gwen Tindula, Sudipta Kumer Mukherjee, Sheikh Muhammad Ekramullah, D M Arman, Joynul Islam, Subrata Kumar Biswas, Benjamin C Warf, David C Christiani, Bernardo Lemos, Liming Liang, Andres Cardenas, Maitreyi Mazumdar

{"title":"Parental arsenic exposure and tissue-specific DNA methylation in Bangladeshi infants with spina bifida.","authors":"Gwen Tindula, Sudipta Kumer Mukherjee, Sheikh Muhammad Ekramullah, D M Arman, Joynul Islam, Subrata Kumar Biswas, Benjamin C Warf, David C Christiani, Bernardo Lemos, Liming Liang, Andres Cardenas, Maitreyi Mazumdar","doi":"10.1080/15592294.2024.2416345","DOIUrl":"10.1080/15592294.2024.2416345","url":null,"abstract":"An emerging hypothesis linking arsenic toxicity involves altered epigenetic mechanisms, such as DNA methylation. In this study, we examined the relationship between parents' arsenic exposure and DNA methylation in tissues obtained from 28 infants with spina bifida from Bangladesh. We analyzed arsenic in parents' toenails using inductively coupled plasma mass spectrometry (ICP-MS). DNA methylation was measured in infants' dural tissue, buccal swabs, and whole blood using the Illumina Infinium MethylationEPIC BeadChip. We performed epigenome-wide association analyses (EWAS) and tested differentially methylated regions (DMRs). In EWAS, DNA methylation at cg24039697 in dural tissue was positively associated (β = 0.59, p = 7.6 × 10-9) with father's toenail arsenic concentrations, adjusting for covariates. We did not identify any CpG sites related to father's arsenic exposure in the other tissues, or any CpG sites related to mother's arsenic exposure. Gene ontology analysis identified many biological pathways of interest, including the Wnt signaling pathways. We identified several DMRs across the tissues related to arsenic exposure that included probes mapping to genes that have previously been identified in studies of neural tube defects. This study emphasizes the potential impact of arsenic exposure in fathers, often understudied in epidemiological studies, on DNA methylation in a unique neurological tissue specific to spina bifida.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2416345"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460921","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}

引用次数: 0

Placental and immune cell DNA methylation reference panel for bulk tissue cell composition estimation in epidemiological studies.

IF 2.9 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-12-08 DOI: 10.1080/15592294.2024.2437275

Kyle A Campbell, Justin A Colacino, John Dou, Dana C Dolinoy, Sung Kyun Park, Rita Loch-Caruso, Vasantha Padmanabhan, Kelly M Bakulski

{"title":"Placental and immune cell DNA methylation reference panel for bulk tissue cell composition estimation in epidemiological studies.","authors":"Kyle A Campbell, Justin A Colacino, John Dou, Dana C Dolinoy, Sung Kyun Park, Rita Loch-Caruso, Vasantha Padmanabhan, Kelly M Bakulski","doi":"10.1080/15592294.2024.2437275","DOIUrl":"10.1080/15592294.2024.2437275","url":null,"abstract":"To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental villous tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated new and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples (n = 36) with robust partial correlation based on the top 30 hyper- and hypomethylated sites identified per cell type. To test deconvolution performance, we evaluated root mean square error in predicting principal components of DNAm variation in 204 external placental samples. We analyzed DNAm profiles (n = 368,435 sites) from 12 cell types: cytotrophoblasts (n = 18), endothelial cells (n = 19), Hofbauer cells (n = 26), stromal cells (n = 21), syncytiotrophoblasts (n = 4), six lymphocyte types (n = 36), and nucleated red blood cells (n = 11). Median cell composition was consistent with placental biology: 60.9% syncytiotrophoblast, 17.3% stromal, 8.8% endothelial, 3.7% cytotrophoblast, 3.7% Hofbauer, 1.7% nucleated red blood cells, and 1.2% neutrophils. Our expanded reference outperformed an existing reference in predicting DNAm variation (PC1, 15.4% variance explained, IQR = 21.61) with cell composition estimates (mean square error of prediction: 8.62 vs. 10.79, p-value < 0.001). This cell type reference can robustly estimate cell composition from whole placental DNAm data to detect important cell types, reveal biological mechanisms, and improve causal inference.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2437275"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793939","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}

引用次数: 0

DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer. 局部前列腺癌男性队列中转移风险的 DNA 甲基化标记。

IF 3.7 3区生物学

Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-03-25 DOI: 10.1080/15592294.2024.2308920

Talar S Habeshian, Kimberly L Cannavale, Jeff M Slezak, Yu-Hsiang Shu, Gary W Chien, XuFeng Chen, Feng Shi, Kimberly D Siegmund, Stephen K Van Den Eeden, Jiaoti Huang, Chun R Chao

{"title":"DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer.","authors":"Talar S Habeshian, Kimberly L Cannavale, Jeff M Slezak, Yu-Hsiang Shu, Gary W Chien, XuFeng Chen, Feng Shi, Kimberly D Siegmund, Stephen K Van Den Eeden, Jiaoti Huang, Chun R Chao","doi":"10.1080/15592294.2024.2308920","DOIUrl":"10.1080/15592294.2024.2308920","url":null,"abstract":"Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997-12/31/2006 who did not receive curative treatments. Cases were those who developed metastasis within 10 years from diagnosis. Controls were selected using density sampling. Ninety-eight candidate genes were selected from functional categories of cell cycle control, metastasis/tumour suppressors, cell signalling, cell adhesion/motility/invasion, angiogenesis, and immune function, and 41 from pluripotency genes. Cancer DNA from diagnostic biopsy blocks were extracted and analysed. Associations of methylation status were assessed using CpG site level and principal components-based analysis in conditional logistic regressions. In 215 cases and 404 controls, 27 candidate genes were found to be statistically significant in at least one of the two analytical approaches. The agreement between the methods was 25.9% (7 candidate genes, including 2 pluripotency markers). The DNA methylation status of several candidate genes was significantly associated with risk of metastasis in untreated localized PCa patients. These findings may inform future risk prediction models for PCa metastasis beyond clinical characteristics.","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2308920"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206525","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}

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