Environmental Epigenetics最新文献

{"title":"Environmental epigenomics and the human imprintome.","authors":"Randy L Jirtle","doi":"10.1093/eep/dvaf029","DOIUrl":"10.1093/eep/dvaf029","url":null,"abstract":"<p><p>Genomic imprinting is a phenomenon in which one parental allele is silenced epigenetically. My research has focused on the role of epigenetics in human health and disease since 1995 when we identified the first tumor suppressor gene that is also imprinted, the <i>IGF2R</i>. Subsequently, by using the agouti viable yellow (A^vy) mouse model, we demonstrated that increased maternal dietary exposure to methyl donors <i>in utero</i> altered offspring phenotype in adulthood by modifying the epigenome, providing a plausible mechanism for the developmental origins of health and disease (DOHaD). Consequently, the field of epigenetics can be thought of as the \"science of hope,\" since personal changes in diet and physical activity can potentially alter the epigenome to prevent chronic disease formation, and potentially, even ameliorate the negative effects of environmental exposures to chemical and physical toxicants. In this perspectives article, I address a series of questions posed about the field of environmental epigenetics, and discuss the role that the environmentally labile <i>cis</i>-acting, imprint regulatory elements in the human genome (i.e. the human imprintome) and the correlated regions of systemic interindividual variation (CoRSIVs) play in disease formation and behavioral development.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf029"},"PeriodicalIF":3.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12573425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cost-effective method for combining the power of genetic and epigenetic selection in animal production.","authors":"Núria Sánchez-Baizán, Marine Herlin, Adrián Millán, Paulino Martínez, María Dolores López Belluga, Francesc Piferrer","doi":"10.1093/eep/dvaf027","DOIUrl":"10.1093/eep/dvaf027","url":null,"abstract":"<p><p>Traditional breeding programs have largely focused on genetics, often overlooking environmental and epigenetic influences on phenotypic variability. Current methods for developing epigenetic biomarkers (EBs) with machine learning (ML) algorithms require extensive data, making them costly and time-intensive. In this study, using a fish as a model, we analysed ~500 000 CpG loci in samples from 60 different families to develop EBs for broodstock selection. To address limited sample sizes at the sequencing stage, we combined careful sample selection, statistical filtering, and various feature selection and ML algorithms. As a result, we identified three heritable CpGs sites in sire sperm associated with three key performance indicators in their offspring: biomass, fast-growing females, and resistance to the masculinizing effects of high temperature. Then, we were able to build a model successfully predicting the best sire broodstock based on DNA methylation levels of these EBs. This model was validated across three independent trials, including one involving an external cohort of fish with differentiated genetic background, thereby confirming its robustness beyond the training population. Yield was increased up to 1.4-fold when including epigenetic selection into the genetic selection program as compared with genetic selection alone. In summary, we present a cost-effective strategy for integrating epigenetic and genetic selection in the context of animal production. Furthermore, this method also can be applied to assess the impact of environmental factors into the broodstock and on samples where obtaining information can be challenging, such as in the study of the epigenetic basis of rare diseases, and the application of epigenetic markers in conservation biology.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf027"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12581941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole methylomes reveal high-altitude-associated methylation at hypoxia and pigmentation genes in South American Indigenous populations.","authors":"Yemko Pryor, Nicola Rambaldi Migliore, Daniel Rivas Alava, Rosalinda Di Gerlando, Dean Herman Tineo Tineo, Leonor Gusmão, Fabricio González-Andrade, Alessandro Achilli, John Lindo","doi":"10.1093/eep/dvaf026","DOIUrl":"10.1093/eep/dvaf026","url":null,"abstract":"<p><p>High-altitude adaptation in Andean populations has traditionally been studied through the lens of genetic variation, with limited exploration of epigenetic mechanisms such as DNA methylation. Here, we present the first whole-methylome data comparing Indigenous populations residing in high-altitude regions of the Ecuadorian Andes to those in low-altitude Peruvian Amazon regions bordering the Andes. By leveraging whole-methylome sequencing rather than methylation arrays, we achieved an unprecedented resolution of epigenetic variation, revealing novel insights into altitude-associated adaptations. We identified significant differentially methylated regions in genes involved in hypoxia response and skin pigmentation that differ from patterns previously observed in high-altitude Tibetan individuals [Lin et al. (Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation. Science China Life Sciences 2023;66:2354-69. https://doi.org/10.1007/s11427-022-2284-8.)]. Our findings highlight the influence that altitude-specific environmental pressures, such as hypoxia and ultraviolet radiation, can have on the epigenetic landscapes observed between human populations. Importantly, we uncovered unique regulatory methylation signatures in the hypoxia response pathways of Andean populations, underscoring a distinct epigenetic trajectory compared to other high-altitude groups. This study represents a step forward in understanding Indigenous American genomic plasticity and demonstrates the value of whole-methylome data over methylation arrays in capturing the complex interplay between epigenetics and the environment. These results support a new approach to studying altitude plasticity and underscore the critical role of epigenetics in shaping population-specific cellular responses in Indigenous communities.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf026"},"PeriodicalIF":3.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modifications and transgenerational inheritance in women victims of violence (EWVV).","authors":"Donato Gemmati, Matteo Villanova, Fabio Scarpellini, Daniela Milani, Rossana Cecchi, Ajay Vikram Singh, Rosa Maria Gaudio, Veronica Tisato","doi":"10.1093/eep/dvaf025","DOIUrl":"10.1093/eep/dvaf025","url":null,"abstract":"<p><p>Female survivors of physical or psychological violence, including sexual violence, report significant long-term consequences defined as post-traumatic stress disorder (PTSD). Among these, depression, affective difficulties, anomalous behaviours, and worsened reproductive health may also affect offspring through transgenerational transmission involving primordial germ cells (PGCs) and/or through social transmission and acquisition of behavioural patterns from parent(s) to children. The concept of epigenomic modification involves several molecular targets that are sensitive to environmental stressors, which tune gene activity and expression. DNA methylation, histone acetylation, ncRNAs, telomere attrition, and mitochondrial dysfunction cooperate in maintaining homeostasis and may affect genes involved in key pathways, such as the hypothalamic-pituitary-adrenal axis, mediating the integrated homeostatic response to stressors. The most investigated genes were those implicated in neuroendocrine stress responses; dopamine, norepinephrine, and serotonin signalling; apoptosis; insulin secretion; neuroplasticity; reproduction; foetal growth; and cancer (e.g. <i>MAOA, BRSK2, ADCYAP1, BDNF, DRD2, IGF2, H19</i>). Additional investigated genes were those involved in other important functions, such as neuropeptide binding, immunoregulation, histone deacetylase/demethylase, inflammatory response, and serotonin uptake, yielding interesting but preliminary or not completely replicated findings (e.g. <i>CRHR1, FKBP5, KDM1A, NR3C1, PRTFDC1</i>, and <i>SLC6A4</i>). The assumption that epigenetic traits induced by negative experiences can be reversed by appropriate social, psychological, and pharmacological interventions has prompted the scientific community to investigate the relationship between epigenetic mechanisms and physical and psychological violence. This can help to identify direct links or epigenetic marks useful for optimizing personalized interventions encompassing the genetic, neuropsychiatric, social, and forensic medicolegal fields. Future research should be conducted with extreme caution to evaluate the long-term effects of such strategies and assess whether the immediate observed effects are maintained.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf025"},"PeriodicalIF":3.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multigenerational inheritance of parasitic stress memory in <i>Drosophila melanogaster</i>.","authors":"Shagufta Khan, Ravina Saini, Runa Hamid, Rakesh K Mishra","doi":"10.1093/eep/dvaf023","DOIUrl":"10.1093/eep/dvaf023","url":null,"abstract":"<p><p>Organisms detect harmful environmental conditions and employ strategies to protect themselves. Additionally, they can communicate these experiences to the next generation or beyond through non-DNA sequence-based mechanisms, known as intergenerational or transgenerational epigenetic inheritance, respectively. Using a specialist larval parasitoid, <i>Leptopilina boulardi</i>, and its host, <i>Drosophila melanogaster</i>, we demonstrate that parental experience of parasitic stress leads to increased survivability in the immediate offspring of the host. Furthermore, we observe that this increased survivability in response to parasitic stress is transmitted transgenerationally when the grandparents, but not the parents, have been exposed to the parasitoid. This increased survivability is primarily inherited through male parents, with one form of effect being enhanced immune priming at the larval stage. Our study suggests that stress exposure during the pre-adult stage of the host provides lifetime benefits for its progeny, enabling them to better cope with future parasitic attacks.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf023"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenome-wide association study of placental co-methylated regions in newborns for prenatal opioid exposure.","authors":"Mandy Meijer, Chaini Konwar, Rebecca Asiimwe, Julia Maclsaac, Katia Ramadori, David Lin, Eric L Garland, Brendan Ostlund, Michael S Kobor, Sheila E Crowell, Elisabeth Conradt","doi":"10.1093/eep/dvaf021","DOIUrl":"10.1093/eep/dvaf021","url":null,"abstract":"<p><p>The increasing incidence of opioid use during pregnancy has led to a rise in the number of infants exposed to opioids in utero. Prenatal opioid exposure may have consequences for health and (neuro)development, including neonatal opioid withdrawal syndrome (NOWS). It is unknown which infants are at greatest risk for NOWS. DNA methylation (DNAm) is an epigenetic mark reflecting both allelic variation and environmental exposures, which may provide biomarkers for prenatal opioid exposure and infant NOWS. The placenta is an accessible, biologically relevant tissue in which to directly investigate the epigenetic effects of prenatal opioid exposure. Therefore, the aims of this study were to examine whether prenatal opioid exposure is associated with differential DNAm, including epigenetic age acceleration (EAA) in the placenta. We performed an epigenome-wide association study based on co-methylated regions and single CpG sites in placental samples from in utero opioid-exposed (<i>n =</i> 19) and nonexposed infants (<i>n</i> = 143), correcting for potential confounders. We did not identify statistically significant differential DNAm profiles, but the strongest associations were found for cg06621211; cg18688392 (<i>ZMIZ1</i>, adjusted <i>P</i> = .068) and cg04460738 (<i>KCNMA1</i>, adjusted <i>P</i> = .068), although effect sizes were very small. One of these DNAm patterns (cg06621211) was in part under control of genetic variants through methylation quantitative trait loci. The involved single nucleotide polymorphism did not show significant associations in recent genome-wide association studies for phenotypes related to substance use, and the finding was not driven by potential co-occurring substance use based on sensitivity analyses. There was also no association between placental EAA and in utero opioid exposure. In conclusion, placental DNAm showed limited associations with in utero opioid exposure and NOWS diagnosis.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf021"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between maternal perceived stress during pregnancy and offspring DNA methylation changes in HPA axis genes at birth in the ECHO Consortium.","authors":"Krystin Jones, Bianca P Acevedo, Lyndsay A Avalos, Brennan H Baker, Nicole R Bush, Claudia Buss, Luke P Grosvenor, Alison E Hipwell, Kristine Marceau, Cindy T McEvoy, Wei Perng, Alexandra D W Sullivan, Irene Tung, Yeyi Zhu, Christine Ladd-Acosta","doi":"10.1093/eep/dvaf024","DOIUrl":"10.1093/eep/dvaf024","url":null,"abstract":"<p><p>Evidence has linked maternal exposure to stress during pregnancy with poor offspring health and neurodevelopmental outcomes. However, the precise mechanism by which this may occur has not been fully elucidated. In this study, we examined whether maternal perceived stress during pregnancy was associated with newborn blood DNA methylation (DNAm) in hypothalamic-pituitary-adrenal axis-related genes (<i>NR3C1, FKBP5</i>, and <i>HSD11B2)</i> in single CpG site and gene-based analyses. We analysed a subset of 661 mother-child pairs from the Environmental Influences on Child Health Outcomes cohort study that met our analytic inclusion criteria. Maternal perceived stress was measured during pregnancy using the perceived stress scale, and newborn DNAm was measured using the Illumina 450K and EPIC Beadchips in cord blood and dried blood spots. Single-site associations were evaluated using linear regression models, and gene-based associations were evaluated using mean burden and variance component tests, adjusted for sociodemographic and lifestyle covariates. Sex-stratified models were used to evaluate sex differential effects. Prenatal perceived stress was statistically significantly associated with newborn DNAm in one CpG site (cg06613263) in <i>NR3C1</i> and with aggregate DNAm in <i>NR3C1</i> and <i>FKBP5</i>. Aggregate DNAm in <i>FKBP5</i> was more strongly associated with prenatal perceived stress in female infants. These results may have important implications for improving offspring health and well-being by providing molecular targets that can be used to identify high-risk individuals and as a basis for developing and evaluating effective behaviour and pharmaceutical interventions.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf024"},"PeriodicalIF":3.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When cells think: a neuro-symbolic view of epigenetic regulation.","authors":"Elia Mario Biganzoli, Valentina Bollati","doi":"10.1093/eep/dvaf022","DOIUrl":"10.1093/eep/dvaf022","url":null,"abstract":"<p><p>Traditionally viewed as a set of switches regulating gene expression, epigenetic mechanisms may also operate as an information-processing system with symbolic and subsymbolic features. In this framework, gene-specific DNA methylation and other localized epigenetic marks act as symbolic 'on/off' signals, while repetitive and noncoding DNA elements form a substrate for probabilistic, distributed responses to environmental stimuli. This hybrid perspective parallels machine-learning approaches, where symbolic representations are combined with subsymbolic methods (e.g. neural networks) to achieve robust learning and adaptation. Here, we propose that epigenetic regulation integrates these two dimensions (i.e. symbolic control and subsymbolic redundancy) to enable cells to adapt to complex environmental challenges, maintain heritable memory of past exposures, and evolve. In this manuscript, we introduce the concept of epigenetic intelligence, clarifying the synergy between discrete, 'symbolic' epigenetic switches (e.g. gene-specific DNA methylation) and the more 'subsymbolic', distributed features of the genome (e.g. repetitive elements methylation). This approach appears to be novel, as existing literature has not explicitly framed epigenetic regulation within a neuro-symbolic artificial intelligence perspective.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf022"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic signatures of phthalate exposure and potential risks: a DNA methylation analysis using Infinium MethylationEPIC BeadChip.","authors":"Ping-Hsun Wu, Shiau-Ching Chen, Chun-Jui Chien, Johnathan Lin, Hsiang-Ying Lee, Yi-Ting Lin, Ting-Chia Weng, Ping-Chi Hsu, Ming-Tsang Wu, Sung-Huan Yu","doi":"10.1093/eep/dvaf020","DOIUrl":"10.1093/eep/dvaf020","url":null,"abstract":"<p><p>Phthalates are common environmental pollutants known to disrupt various regulatory systems and are associated with several health issues, such as impaired immune response, developmental toxicity, hormonal disruption, and type 2 diabetes. Epigenetic modifications, such as DNA methylation, can serve as early indicators of environmental toxicant exposure due to their rapid alteration in response to varying environmental factors without altering the underlying DNA sequence. To investigate the impact of phthalate exposure on human health and the affected regulatory mechanisms, this study analysed a DNA methylation dataset generated using the Illumina Infinium MethylationEPIC BeadChip (EPIC BeadChip) array, along with the concentrations of 15 urinary phthalate metabolites from 389 participants. The results revealed sex-specific differences in phthalate concentrations, with females exhibiting relatively higher levels than males. These differences may reflect a combination of factors, including lifestyle behaviours and potential differences in exposure sources. Furthermore, differentially methylated CpG sites (DMCs) were identified only in the mono-ethylhexyl phthalate (MEHP) dataset, where a total of 53 DMCs were detected, including 11 that were consistently detected across multiple MEHP concentration comparisons. Additionally, the functional analysis showed that these DMCs are primarily involved in protein and nucleotide binding, immune response, ion channel regulation, and membrane-associated pathways. This study provides high-potential phthalate-related methylation markers, their associated genes, and the functions they are involved in. These findings offer valuable insights for the research on environmental toxicants and epigenetics, while supporting clinical applications related to phthalates.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf020"},"PeriodicalIF":3.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation signatures of arsenic exposure and obesity.","authors":"Natália Yumi Noronha, Guilherme da Silva Rodrigues, Lígia Moriguchi Watanabe, Isabella Harumi Yonehara Noma, Jean-Baptiste Cazier, Chanachai Sae-Lee, Pitaksin Chitta, Vanessa Aparecida Batista Pereira, Marcela Augusta de Souza Pinhel, Luísa Maria Diani, Fernando Barbosa, Torsten Plösch, Carla Barbosa Nonino","doi":"10.1093/eep/dvaf019","DOIUrl":"10.1093/eep/dvaf019","url":null,"abstract":"<p><p>Emerging evidence suggests a link between environmental pollution and epigenetic alterations, prompting the need for comprehensive investigations into the relationship between pollutants and health conditions in human populations. This study investigates the interplay between obesity and exposure to toxic metals, examining clinical, serum metal concentrations, and epigenetic signatures. Our approach included serum metal concentration analysis by inductively coupled plasma mass spectrometry and epigenetic analysis using 450k Illumina BeadChips data. Singular value decomposition and linear regression models were used to identify metal associations with DNA methylation. Marked differences were evident in weight, body mass index, glycaemia, High Density Lipoprotein cholesterol (HDL-c), and triglycerides between patients with obesity and without obesity. Metal serum concentrations revealed higher arsenic levels in participants with obesity, while elevated mercury concentrations were found in individuals without obesity. Epigenetic analysis identified 2045 arsenic-associated differentially methylated positions (DMPs) in individuals with obesity, including 57 hypermethylated and 159 hypomethylated sites in promoter regions. These DMPs demonstrated direct associations of arsenic exposure, and traits such as insufficient sleep, smoking, and diseases such as gestational diabetes. Functional enrichment analysis (using traits, gene ontology, and KEGG pathways) highlighted pathways linking obesity and arsenic exposure, specifically the Wnt and TNF signalling pathways. Additionally, hypermethylated sites were linked with cancer, rheumatoid arthritis, and gestational diabetes, emphasizing the intricate relationship between these conditions. Notably, <i>ABCF1</i> and <i>BRCA1</i> showed significant differences in methylation associated with arsenic and obesity. The findings provide valuable insights into unravelling the connections between obesity and arsenic exposure, contributing to understand the potential molecular mechanisms and pathways in these intersecting fields.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf019"},"PeriodicalIF":3.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}