Environmental Epigenetics最新文献

{"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}

{"title":"Molecular responses of chicken embryos to maternal heat stress through DNA methylation and gene expression: a pilot study.","authors":"Keyvan Karami, Jules Sabban, Chloé Cerutti, Guillaume Devailly, Sylvain Foissac, David Gourichon, Alexandre Hubert, Jean-Noël Hubert, Sophie Leroux, Tatiana Zerjal, Sandrine Lagarrigue, Frédérique Pitel","doi":"10.1093/eep/dvaf009","DOIUrl":"10.1093/eep/dvaf009","url":null,"abstract":"<p><p>Climate change, with its repercussions on agriculture, is one of the most important adaptation challenges for livestock production. Poultry production is a major source of proteins for human consumption all over the world. With a growing human population, improving poultry's adaptation to environmental constraints becomes critical. Extensive evidence highlights the influence of environmental variations on epigenetic modifications. The aim of this paper is therefore to explore chickens' molecular response to maternal heat stress. We employed Reduced Representation Bisulfite Sequencing to generate genome-wide single-base resolution DNA methylation profiling and RNA sequencing to profile the transcriptome of the brains of embryos hatched from dams reared under either heat stress (32°C) or thermoneutrality (22°C). We detected 289 significant differentially methylated CpG sites (DMCs) and one differentially methylated region (DMR) between heat stressed and control groups. These DMCs were associated with 357 genes involved in processes such as cellular response to stimulus, developmental processes, and immune function. In addition, we identified 11 genes differentially expressed between the two groups of embryos, and identified ATP9A as a target gene of maternal heat stress on offspring. This study provides a body of fundamental knowledge on adaptive mechanisms concerning heat tolerance in chickens.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf009"},"PeriodicalIF":4.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282952","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":"Deciphering differences in DNA methylation and transcriptome profiles of oocytes from pigs with high and low developmental competence.","authors":"Laura Abril-Parreño, Jordana S Lopes, Jon Romero-Aguirregomezcorta, Antonio Galvao, Gavin Kelsey, Pilar Coy","doi":"10.1093/eep/dvaf018","DOIUrl":"10.1093/eep/dvaf018","url":null,"abstract":"<p><p><i>In vitro</i> maturation (IVM) is a critical step in animal <i>in vitro</i> embryo production, yet oocytes matured <i>in vitro</i> often exhibit lower developmental competence than their <i>in vivo</i> counterparts. However, the molecular mechanisms behind this observation remain unclear. This study investigated the gene expression and DNA methylation profiles in porcine oocytes with different developmental competencies. To study these differences, we used as a model oocytes from prepubertal gilts (IVM) and sows (<i>in vivo</i> matured) and assessed their developmental competence up to the blastocyst stage. We also examined their gene expression and DNA methylation profiles at single-cell resolution using RNA sequencing and bisulfite sequencing. Oocytes were obtained by aspiration of either ovarian follicles between 3 and 6 mm diameter, and the subsequent IVM, or ovarian follicles from 8 to 10 mm diameter, with no need for maturation (<i>in vivo</i> matured oocytes). Cleavage rates (58.2 ± 3.0 and 45.7 ± 4.4) and blastocyst rates (31.4 ± 3.7 and 47.5 ± 6.6) for IVM and <i>in vivo</i> groups differed significantly. Using the <i>in vivo</i> group as a reference, IVM oocytes had 1297 downregulated and 476 upregulated differentially expressed genes (DEGs), with upregulated DEGs associated with organelle organization and cell cycle processes, and downregulated genes involved in protein synthesis and metabolomic processes. While global DNA methylation levels were similar between groups, a few differentially methylated regions were found in CpG islands, promoters, and coding regions. Our integrative analysis identified key methylated regions and genes that distinguish each group, suggesting that both donor age and maturation conditions significantly influence gene expression regulation in oocytes with different developmental competencies.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf018"},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039390","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":"Mapping heat stress-induced core histone post-translational modifications in <i>Acropora cervicornis</i>.","authors":"Cassandra N Fuller, Sabrina Mansoor, Santiago J Guzman, Lilian Valadares Tose, Serena Hackerott, Javier Rodriguez-Casariego, Jose M Eirin-Lopez, Francisco Fernandez-Lima","doi":"10.1093/eep/dvaf017","DOIUrl":"10.1093/eep/dvaf017","url":null,"abstract":"<p><p>Histone post-translational modifications (PTMs) participate in the dynamic regulation of chromatin structure and function, through their chemical nature and specific location within the histone sequence. Alternative analytical approaches for histone PTM studies are required to facilitate the differentiation between ubiquitously present isomers and the detection of low-abundance PTMs Here, we report a high-sensitivity bottom-up method based on nano-liquid chromatography (nLC), trapped ion mobility spectrometry (TIMS), data-dependent acquisition (DDA), parallel accumulation-serial fragmentation (PASEF), and high-resolution time-of-flight tandem mass spectrometry (ToF-MS/MS) for the analysis of histone PTMs. This method was tested in a threatened coral species, the staghorn coral <i>Acropora cervicornis</i>, during an episode of acute thermal stress. The obtained results allowed for the identification of PTM changes in core histones involved in the coral's heat response. Compared to traditional LC-MS/MS approaches, the incorporation of TIMS and ddaPASEF MS/MS resulted in a highly specific and sensitive method with a wide dynamic range (6 orders of magnitude). This depth of analysis allows for the simultaneous measurement of low-abundance PTM signatures relative to the unmodified form. An added advantage is the ability to mass- and mobility-isolate prior to peptide sequencing, resulting in higher confidence identification of epigenetic markers associated with heat stress in corals (e.g. increased H4 4-17 with 2ac and 3ac, and decreases in H4 4-17 K12ac, K16ac, H4 K20me₂, and H2A K5ac, K7ac, K9ac, K12ac, K14ac, and K74ac).</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf017"},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039485","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":"Immediate and durable effects of maternal tobacco consumption on placental DNA methylation: a replication and discovery study.","authors":"Chloé Masdoumier, Lucile Broséus, Florent Chuffart, Olivier François, Ariane Guilbert, Barbara Heude, Saadi Khochbin, Sophie Rousseaux, Emie Seyve, Muriel Tafflet, Jorg Tost, Aurélie Nakamura, Johanna Lepeule","doi":"10.1093/eep/dvaf016","DOIUrl":"10.1093/eep/dvaf016","url":null,"abstract":"<p><p>An increasing number of epigenome-wide association studies report tobacco smoking-associated DNA methylation levels. However, comprehensive replication studies remain scarce, particularly in placenta, despite their crucial interest in such a large-scale context. Using DNA methylation data from the EPIC array of 341 new placentas (85 smokers, 219 non-smokers, and 37 former smokers) from the EDEN cohort, we used a candidate approach to replicate maternal smoking-associated CpGs and regions previously identified using the 450K array, and an exploratory approach to discover new associations within EPIC-specific CpGs. Smoking-associated changes in DNA methylation in CpGs and regions were classified as either transient or persistent (indicating epigenetic memory), depending on the stability of their association with smoking status. Among candidate loci, 38% of probes and 9% of regions were replicated, providing robust evidence of effects of prenatal smoke exposure on methylation patterns of these loci. <i>LEKR1</i> was the top hit in both the initial and replication studies. Most of the replicated loci were transient CpGs (i.e. current smokers), while persistent CpGs (i.e. former smokers) remained scarce and somewhat inconsistent with previous findings. The additional exploratory analysis identified 733 novel probes and 75 novel regions, including 18% and 30% of transient loci, respectively. Results suggested that most of the effects were related to <i>in utero</i> exposure only, supporting pregnant women's efforts to quit smoking. This replication study also evidences the importance of reproducible work in omic investigations to provide a more in-depth and robust understanding of the effects of environmental exposures on health biomarkers..</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"11 1","pages":"dvaf016"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029399","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}