Epigenetics Insights最新文献

{"title":"Association of Asthma and Rhinitis with Epigenetics of Coronavirus Related Genes.","authors":"Aniruddha Rathod,&nbsp;Rutu Rathod,&nbsp;Hongmei Zhang,&nbsp;Parnian Kheirkhah Rahimabad,&nbsp;Wilfried Karmaus,&nbsp;Hasan Arshad","doi":"10.1177/25168657211039224","DOIUrl":"https://doi.org/10.1177/25168657211039224","url":null,"abstract":"<p><strong>Introduction: </strong>Susceptibility factors for coronavirus disease 2019 (COVID-19) include sex and medical conditions such as asthma and rhinitis. DNA methylation (DNAm) is associated with asthma, rhinitis, and several viruses. We examined associations of asthma/rhinitis with DNAm at CpGs located on coronavirus related genes, and if these associations were sex-specific.</p><p><strong>Methods: </strong>In total, n = 242 subjects aged 26 years from the Isle of Wight Birth Cohort were included in the study. Linear regressions were used to examine sex specific and non-specific associations of DNAm at CpGs on coronavirus related genes with asthma/rhinitis status. Associations of DNAm with gene expression in blood were assessed for functional relevance of identified CpGs.</p><p><strong>Results: </strong>Statistically significant interaction effects of asthma or rhinitis with sex were identified at 40 CpGs for asthma and 27 CpGs for rhinitis. At 21 CpGs, DNAm was associated with asthma, and at 45 CpGs with rhinitis, regardless of sex. Assessment of functional relevance of the identified CpGs indicated a potential of epigenetic regulatory functionality on gene activity at 14 CpGs for asthma and 17 CpGs for rhinitis, and of those 6 CpGs for asthma and 7 CpGs for rhinitis were likely to be sex-specific.</p><p><strong>Conclusion: </strong>Subjects with asthma/rhinitis may have altered susceptibility to COVID-19 due to changes in their DNAm associated with these conditions. Sex specificity on association of asthma/rhinitis with DNAm at certain CpGs, and on the association of DNAm at asthma/rhinitis-linked CpGs with gene expression have the potential to explain the reported sex-specificity in COVID-19 morbidity and mortality.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211039224"},"PeriodicalIF":2.2,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/a4/10.1177_25168657211039224.PMC8485269.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39484589","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 at Birth is Associated with Childhood Serum Immunoglobulin E Levels.","authors":"Luhang Han,&nbsp;Akhilesh Kaushal,&nbsp;Hongmei Zhang,&nbsp;Latha Kadalayil,&nbsp;Jiasong Duan,&nbsp;John W Holloway,&nbsp;Wilfried Karmaus,&nbsp;Pratik Banerjee,&nbsp;Shih-Fen Tsai,&nbsp;Hui-Ju Wen,&nbsp;Syed Hasan Arshad,&nbsp;Shu-Li Wang","doi":"10.1177/25168657211008108","DOIUrl":"https://doi.org/10.1177/25168657211008108","url":null,"abstract":"<p><p>Immunoglobulin E (IgE) is known to play an important role in allergic diseases. Epigenetic traits acquired due to modification of deoxyribonucleic acid (DNA) methylation (DNAm) in early life may have phenotypic consequences through their role in transcriptional regulation with relevance to the developmental origins of diseases including allergy. However, epigenome-scale studies on the longitudinal association of cord blood DNAm with IgE over time are lacking. Our study aimed to examine the association of DNAm at birth with childhood serum IgE levels during early life. Genome-scale DNAm and total serum IgE measured at birth, 5, 8, and 11 years of children in the Taiwan Maternal and Infant Cohort Study were included in the study in the discovery stage. Linear mixed models were implemented to assess the association between cord blood DNAm at ~310K 5'-cytosine-phosphate-guanine-3' (CpG) sites with repeated IgE measurements, adjusting for cord blood IgE. Identified statistically significant CpGs (at a false discovery rate, FDR, of 0.05) were further tested in an independent replication cohort, the Isle of Wight (IoW) birth cohort. We mapped replicated CpGs to genes and conducted gene ontology analysis using ToppFun to identify significantly enriched pathways and biological processes of the genes. Cord blood DNAm of 273 CpG sites were significantly (FDR = 0.05) associated with IgE levels longitudinally. Among the identified CpGs available in both cohorts (184 CpGs), 92 CpGs (50%) were replicated in the IoW in terms of consistency in direction of associations between DNA methylation and IgE levels later in life, and 16 of the 92 CpGs showed statistically significant associations (<i>P</i> < .05). Gene ontology analysis identified 4 pathways (FDR = 0.05). The identified 16 CpG sites had the potential to serve as epigenetic markers associated with later IgE production, beneficial to allergic disease prevention and intervention.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211008108"},"PeriodicalIF":2.2,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/25168657211008108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38819612","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":"Relationships among Inorganic Arsenic, Nutritional Status CpG Methylation and microRNAs: A Review of the Literature.","authors":"Abhishek Venkatratnam,&nbsp;Carmen A Marable,&nbsp;Arjun M Keshava,&nbsp;Rebecca C Fry","doi":"10.1177/2516865721989719","DOIUrl":"https://doi.org/10.1177/2516865721989719","url":null,"abstract":"<p><p>Inorganic arsenic is a naturally occurring toxicant that poses a significant and persistent challenge to public health. The World Health Organization has identified many geographical regions where inorganic arsenic levels exceed safe limits in drinking water. Numerous epidemiological studies have associated exposure to inorganic arsenic with increased risk of adverse health outcomes. Randomized clinical trials have shown that nutritional supplementation can mitigate or reduce exacerbation of exposure-related effects. Although a growing body of evidence suggests that epigenetic status influences toxicity, the relationships among environmental exposure to arsenic, nutrition, and the epigenome are not well detailed. This review provides a comprehensive summary of findings from human, rodent, and in vitro studies highlighting these interactive relationships.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865721989719"},"PeriodicalIF":2.2,"publicationDate":"2021-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865721989719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25391949","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":"Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States.","authors":"Jaclyn M Goodrich,&nbsp;Melissa A Furlong,&nbsp;Alberto J Caban-Martinez,&nbsp;Alesia M Jung,&nbsp;Ken Batai,&nbsp;Timothy Jenkins,&nbsp;Shawn Beitel,&nbsp;Sally Littau,&nbsp;John Gulotta,&nbsp;Darin Wallentine,&nbsp;Jeff Hughes,&nbsp;Charles Popp,&nbsp;Miriam M Calkins,&nbsp;Jefferey L Burgess","doi":"10.1177/25168657211006159","DOIUrl":"https://doi.org/10.1177/25168657211006159","url":null,"abstract":"<p><p>Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw <i>P</i>-value <.05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate (<i>q</i>-value <.05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at <i>q</i> < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene <i>SULT1C2</i> had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies (<i>FOXK2, GYLTL1B, ZBTB16, ARHGEF10</i>, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"14 ","pages":"25168657211006159"},"PeriodicalIF":2.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/25168657211006159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10768648","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":"Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy.","authors":"Sultan Abda Neja","doi":"10.1177/2516865720964808","DOIUrl":"https://doi.org/10.1177/2516865720964808","url":null,"abstract":"<p><p>Aberrant promoter DNA hypermethylation is a typical characteristic of cancer and it is often seen in malignancies. Recent studies showed that regulatory cis-elements found up-stream of many tumor suppressor gene promoter CpG island (CGI) attract DNA methyltransferases (DNMT) that hypermethylates and silence the genes. As epigenetic alterations are potentially reversible, they make attractive targets for therapeutic intervention. The currently used decitabine (DAC) and azacitidine (AZA) are DNMT inhibitors that follow the passive demethylation pathway. However, they lead to genome-wide demethylation of CpGs in cells, which makes difficult to use it for causal effect analysis and treatment of specific epimutations. Demethylation through specific demethylase enzymes is thus critical for epigenetic resetting of silenced genes and modified chromatins. Yet DNA-binding factors likely play a major role to guide the candidate demethylase enzymes upon its fusion. Before the advent of clustered regulatory interspaced short palindromic repeats (CRISPR), both zinc finger proteins (ZNFs) and transcription activator-like effector protein (TALEs) were used as binding platforms for ten-eleven translocation (TET) enzymes and both systems were able to induce transcription at targeted loci in an <i>in vitro</i> as well as <i>in vivo</i> model. Consequently, the development of site-specific and active demethylation molecular trackers becomes more than hypothetical to makes a big difference in the treatment of cancer in the future. This review is thus to recap the novel albeit distinct studies on the potential use of site-specific demethylation for the development of epigenetic based cancer therapy.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720964808"},"PeriodicalIF":2.2,"publicationDate":"2020-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720964808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39827856","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":"<i>E-Cadherin, NFATC3</i>, and <i>PLP2</i> Are Differentially Methylated in Multiple Cancers.","authors":"Mary J Lotesto,&nbsp;Christopher J Wallace,&nbsp;Stacey L Raimondi","doi":"10.1177/2516865720964802","DOIUrl":"https://doi.org/10.1177/2516865720964802","url":null,"abstract":"<p><p>It is well documented that cancer cells have abnormal methylation patterns often caused by faulty methylating machinery. Specifically, <i>E-cadherin, NFATC3</i>, and <i>PLP2</i> are 3 genes known to be aberrantly methylated in cancer cells. These genes are well documented for their role in signaling pathways involved with cell proliferation, adhesion, migration, and other signs of tumor progression. Therefore, changes in gene expression of <i>CDH1, NFATC3</i>, and <i>PLP2</i> due to aberrant methylation can lead to profound changes in cellular function and tumor formation. In order to ensure that previous <i>in vitro</i> and <i>in vivo</i> methylation studies match what is observed in the clinic, we utilized a bioinformatics approach to complete an extensive analysis of methylation patterns of these 3 genes, analyzing over 5000 patient samples, across all cancers for which both normal and tumor tissues were available. Specifically, we analyzed overall and site-specific methylation patterns, at CpG islands and shores, of all 3 genes across 14 cancer types. Furthermore, we compared these methylation levels in normal and tumor samples of both matched and unmatched patient samples in order to determine any differences between groups. Finally, we examined whether an aberrant DNA methyltransferase, <i>DNMT3B7</i>, known to be expressed in cancer cells and to alter methylation patterns <i>in vitro</i> correlated with altered overall and site-specific methylation of <i>CDH1, NFATC3</i>, and <i>PLP2</i> in these patient samples. Our results indicate that methylation patterns of <i>CDH1</i> and <i>NFATC3</i> were unexpectedly varied across tumors, contrary to previous studies performed <i>in vitro</i>, while <i>PLP2</i> showed the expected hypomethylation pattern in tumor tissues. We also observed some correlation between <i>DNMT3B7</i> expression and methylation patterns of these genes, but patterns were inconsistent. Taken together, these results emphasize the necessity for <i>in vivo</i> and patient studies rather than a complete reliance on <i>in vitro</i> data and provide multiple areas of future research.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720964802"},"PeriodicalIF":2.2,"publicationDate":"2020-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720964802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38593823","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 of Endoglin Pathway Genes in Pregnant Women With and Without Preeclampsia.","authors":"Allison H Rietze,&nbsp;Yvette P Conley,&nbsp;Dianxu Ren,&nbsp;Cindy M Anderson,&nbsp;James M Roberts,&nbsp;Arun Jeyabalan,&nbsp;Carl A Hubel,&nbsp;Mandy J Schmella","doi":"10.1177/2516865720959682","DOIUrl":"https://doi.org/10.1177/2516865720959682","url":null,"abstract":"<p><strong>Objective: </strong>We compared blood-based DNA methylation levels of endoglin (<i>ENG</i>) and transforming growth factor beta receptor 2 (<i>TGFβR2</i>) gene promoter regions between women with clinically-overt preeclampsia and women with uncomplicated, normotensive pregnancies.</p><p><strong>Methods: </strong>We used EpiTect Methyl II PCR Assays to evaluate DNA methylation of CpG islands located in promoter regions of <i>ENG</i> (CpG Island 114642) and <i>TGFβR2</i> (CpG Island 110111). Preeclampsia was diagnosed based on blood pressure, protein, and uric acid criteria. N = 21 nulliparous preeclampsia case participants were 1:1 frequency matched to N = 21 nulliparous normotensive control participants on gestational age at sample collection (±2 weeks), smoking status, and labor status at sample collection. Methylation values were compared between case and control participant groups [(<i>ENG</i> subset: n = 20 (9 cases, 11 controls); <i>TGFβR2</i> subset: n = 28 (15 cases, 13 controls)].</p><p><strong>Results: </strong>The majority of the preeclampsia cases delivered at ⩾34 weeks' gestation (83%). Average methylation levels for <i>ENG</i> ([M ± (SD)]; Case Participant Group = 6.54% ± 4.57 versus Control Participant group = 4.81% ± 5.08; <i>P</i> = .102) and <i>TGFβR2</i> (Case Participant Group = 1.50% ± 1.37 vs Control Participant Group = 1.70% ± 1.40; <i>P</i> = .695) promoter CpG islands did not differ significantly between the participant groups. Removal of 2 extreme outliers in the <i>ENG</i> analytic subset revealed a trend between levels of <i>ENG</i> methylation and pregnancy outcome (Case Participant Group = 5.17% ± 2.16 vs Control Participant Group = 3.36% ± 1.73; <i>P</i> = .062).</p><p><strong>Conclusion: </strong>Additional epigenetic studies that include larger sample sizes, investigate preeclampsia subtypes, and capture methylation status of CpG island shores and shelves are needed to further inform us of the potential role that <i>ENG</i> and <i>TGFβR2</i> DNA methylation plays in preeclampsia pathophysiology.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720959682"},"PeriodicalIF":2.2,"publicationDate":"2020-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720959682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38527886","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":"Influence of Woodsmoke Exposure on Molecular Mechanisms Underlying Alzheimer's Disease: Existing Literature and Gaps in Our Understanding.","authors":"Adam Schuller,&nbsp;Luke Montrose","doi":"10.1177/2516865720954873","DOIUrl":"https://doi.org/10.1177/2516865720954873","url":null,"abstract":"<p><p>Woodsmoke poses a significant health risk as a growing component of ambient air pollution in the United States. While there is a long history of association between woodsmoke exposure and diseases of the respiratory, circulatory, and cardiovascular systems, recent evidence has linked woodsmoke exposure to cognitive dysfunction, including Alzheimer's disease dementia. Alzheimer's disease is a progressive neurodegenerative disorder with largely idiopathic origins and no known cure. Here, we explore the growing body of literature which relates woodsmoke-generated and ambient air pollution particulate matter exposure to Alzheimer's disease (AD) onset or exacerbation, in the context of an inflammation-centric view of AD. Epigenetic modifications, specifically changes in DNA methylation patterns, are well documented following woodsmoke exposure and have been shown to influence disease-favoring inflammatory cascades, induce oxidative stress, and modulate the immune response in vitro, in vivo, and in humans following exposure to air pollution. Though the current status of the literature does not allow us to draw definitive conclusions linking these events, this review highlights the need for additional work to fill gaps in our understanding of the directionality, causality, and susceptibility throughout the life course.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720954873"},"PeriodicalIF":2.2,"publicationDate":"2020-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720954873","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38418597","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":"The Role of DNA Methylation in Transcriptional Regulation of Pro-Nociceptive Genes in Rat Trigeminal Ganglia.","authors":"Guang Bai,&nbsp;Holly Ross,&nbsp;Youping Zhang,&nbsp;KiSeok Lee,&nbsp;Jin Y Ro","doi":"10.1177/2516865720938677","DOIUrl":"https://doi.org/10.1177/2516865720938677","url":null,"abstract":"<p><p>Epigenetic modulation by DNA methylation is associated with aberrant gene expression in sensory neurons, which consequently leads to pathological pain responses. In this study, we sought to investigate whether peripheral inflammation alters global DNA methylation in trigeminal ganglia (TG) and results in abnormal expression of pro-nociceptive genes. Our results show that peripheral inflammation remotely reduced the level of global DNA methylation in rat TG with a concurrent reduction in <i>DNMT1</i> and <i>DNMT3a</i> expression. Using unbiased steps, we selected the following pro-nociceptive candidate genes that are potentially regulated by DNA methylation: <i>TRPV1, TRPA1, P2X3</i>, and <i>PIEZO2</i>. Inhibition of DNMT with 5-Aza-dC in dissociated TG cells produced dose-dependent upregulation of <i>TRPV1, TRPA1</i>, and <i>P2X3</i>. Systemic treatment of animals with 5-Aza-dC significantly increased the expression of <i>TRPV1, TRPA1</i>, and <i>PIEZO2</i> in TG. Furthermore, the overexpression of DNMT3a, as delivered by a lentiviral vector, significantly downregulated <i>TRPV1</i> and <i>PIEZO2</i> expression and also reliably decreased <i>TRPA1</i> and <i>P2X3</i> transcripts. MeDIP revealed that this overexpression also significantly enhanced methylation of CGIs associated with <i>TRPV1</i> and <i>TRPA1</i>. In addition, bisulfite sequencing data indicated that the CGI associated with <i>TRPA1</i> was methylated in a pattern catalyzed by DNMT3a. Taken together, our results show that all 4 pro-nociceptive genes are subject to epigenetic modulation via DNA methylation, likely via DNMT3a under inflammatory conditions. These findings provide the first evidence for the functional importance of DNA methylation as an epigenetic factor in the transcription of pro-nociceptive genes in TG that are implicated in pathological orofacial pain responses.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720938677"},"PeriodicalIF":2.2,"publicationDate":"2020-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720938677","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38418158","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":"Paternal DNA Methylation May Be Associated With Gestational Age at Birth.","authors":"Rui Luo,&nbsp;Nandini Mukherjee,&nbsp;Su Chen,&nbsp;Yu Jiang,&nbsp;S Hasan Arshad,&nbsp;John W Holloway,&nbsp;Anna Hedman,&nbsp;Olena Gruzieva,&nbsp;Ellika Andolf,&nbsp;Goran Pershagen,&nbsp;Catarina Almqvist,&nbsp;Wilfried Jj Karmaus","doi":"10.1177/2516865720930701","DOIUrl":"https://doi.org/10.1177/2516865720930701","url":null,"abstract":"<p><strong>Background: </strong>How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites.</p><p><strong>Methods: </strong>Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC.</p><p><strong>Results: </strong>Analysis of DNAm of fathers collected around their partner's pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin (<i>PCDH</i>) gene clusters were associated with gene expression of <i>PCDH</i> in F2 cord blood.</p><p><strong>Conclusions: </strong>Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720930701"},"PeriodicalIF":2.2,"publicationDate":"2020-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720930701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38411572","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}