'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Sat, 05 Jul 2025 08:06:46 EDT Sat, 05 Jul 2025 08:06:46 EDT jirtle@radonc.duke.edu james001@jirtle.com Comparative analysis of statistical and deep learning-based multi-omics integration for breast cancer subtype classification. Omran MM, Emam M, Gamaleldin M, Abushady AM, Elattar MA, El-Hadidi M
J Transl Med (Jul 2025)

Breast cancer (BC) is a critical cause of cancer-related death globally. The heterogeneity of BC subtypes poses challenges in understanding molecular mechanisms, early diagnosis, and disease management. Recent studies suggest that integrating multi-omics layers can significantly enhance BC subtype identification. However, evaluating different multi-omics integration methods for BC subtyping remains ambiguous.]]> Wed, 31 Dec 1969 19:00:00 EST Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome. Wang SE, Cheng Y, Lim J, Jang MA, Forrest EN, Kim Y, Donahue M, Jo S, Qiao SN, Lee DE, Hong JY, Xiong Y, Jin J, Wang S, Jiang YH
Nat Commun (Jul 2025)

Prader-Willi Syndrome (PWS) is caused by the loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain. We previously discovered that euchromatic histone lysine N-methyltransferase-2 (EHMT2/G9a) inhibitors are capable of un-silencing PWS-associated genes by restoring their expression from the maternal chromosome. Here, in mice lacking the Ehmt2 gene, we document un-silencing of the imprinted Snrpn/Snhg14 gene on the maternal chromosome in the late embryonic and postnatal brain. Using PWS and Angelman syndrome patient derived cells with either paternal or maternal deletion of 15q11.2-q13, we have found that chromatin of maternal PWS-IC is closed and has compact 3D folding confirmation. We further show that a distinct noncoding RNA (TSS4-280118) preferentially transcribed from the upstream of the PWS-IC of maternal chromosome interacts with EHMT2 and forms a heterochromatin complex in CIS on the maternal chromosome. Inactivation of TSS4-280118 by CRISPR/Cas9 editing results in unsilencing of the expression of SNRPN and SNORD116 from the maternal chromosome. Taken together, these findings demonstrate that allele-specific recruitment of EHMT2 is required to maintain the maternal imprints. Our findings provide mechanistic insights and support a model for imprinting maintenance of the PWS imprinted domain.]]> Wed, 31 Dec 1969 19:00:00 EST The myoblast methylome: multiple types of associations with chromatin and transcription. Sen S, Lacey M, Baribault C, Ponnaluri VKC, Esteve PO, Ehrlich KC, Meletta M, Pradhan S, Ehrlich M
Epigenetics (Dec 2025)

Epigenetic changes are implicated in development, repair, and physiology of postnatal skeletal muscle (SkM). We generated methylomes for human myoblasts (SkM progenitor cells) and determined myoblast differentially methylated regions (DMRs) for comparison to the epigenomics and transcriptomics of diverse cell types. Analyses were from global genomic and single-gene perspectives and included reporter gene assays. One atypical finding was the association of promoter-adjacent hypermethylation in myoblasts with transcription turn-on, but at downmodulated levels, for certain genes (., and ). In contrast, brain-specific was in repressed chromatin and silent in most cell types but linked to hypermethylated DMRs specifically in myoblasts. The -linked DMRs might be needed because of the overlapping or nearby binding of myogenic differentiation protein 1 (MYOD). We found genome-wide overlap of DMRs with MYOD or CCCTC-binding factor (CTCF) binding sites in myoblasts that is consistent with the importance of MYOD, as well as CTCF, in organizing myoblast transcription-enhancing chromatin interactions. We also observed some gene upregulation correlated with a special association of regional DNA hypomethylation with H3K36me3, H3K27ac, and H3K4me1 enrichment. Our study highlights unusual relationships between epigenetics and gene expression that illustrate the interplay between DNA methylation and chromatin epigenetics in the regulation of transcription.]]> Wed, 31 Dec 1969 19:00:00 EST Comprehensive pan-cancer analysis of NLRs family as prognostic and immunity markers based on multi-omics data. Wen X, Cui M, Zhang J, Huang H
Discov Oncol (Jul 2025)

Members of the NOD-like receptors(NLRs)gene family members involved in inflammasome formation have been implicated in cancer initiation, development, progression, angiogenesis, and invasion. This study comprehensively investigated the role of NLRs in cancer through multi-omics analysis, which is of great necessity for a deeper understanding of the pathogenesis of cancer, improvement of cancer prognosis assessment, promotion of drug development, and advancement of precision medicine.]]> Wed, 31 Dec 1969 19:00:00 EST Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. Martin CL, Chen J, D'Alessio AS, Ward-Caviness CK, Ye A, Lodge EK, Ghastine L, Dhingra R, Jima DD, Murphy SK, Hoyo C
Epigenetics (Dec 2025)

Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.]]> Wed, 31 Dec 1969 19:00:00 EST Rhabdomyosarcoma fusion oncoprotein initially pioneers a neural signature in vivo. Kucinski J, Tallan A, Taslim C, Vontell AM, Silvius KM, Wang M, Cannon MV, Stanton BZ, Kendall GC
Cell Rep (Jul 2025)

Fusion-positive rhabdomyosarcoma is an aggressive pediatric cancer molecularly characterized by arrested myogenesis. The defining genetic driver, PAX3::FOXO1, encodes a chimeric gain-of-function transcription factor. An incomplete understanding of the in vivo chromatin regulatory mechanisms of PAX3::FOXO1 has hindered therapeutic development. Here, we establish a PAX3::FOXO1 zebrafish injection model and a semi-automated ChIP-seq normalization strategy to evaluate how PAX3::FOXO1 initially interfaces with and modulates chromatin in a developmental context. We find that PAX3::FOXO1 interacts with inaccessible chromatin through partial/homeobox motif recognition consistent with pioneering activity. However, PAX3::FOXO1-genome binding through a composite paired box/homeobox motif alters chromatin accessibility and redistributes H3K27ac to activate neural transcriptional programs. We uncover neural signatures that are highly representative of clinical rhabdomyosarcoma gene expression programs that are enriched following chemotherapy. Overall, we identify partial/homeobox motif recognition as a key mode for PAX3::FOXO1 pioneer function and identify neural signatures as a potentially critical PAX3::FOXO1 tumor initiation event.]]> Wed, 31 Dec 1969 19:00:00 EST use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes. Mmatli M, Mbelle NM, Fourie B, Osei Sekyere J
Virulence (Dec 2025)

Whole-genome sequencing, transcriptomic profiling, and epigenomic analyses were performed. Phenotypic assays were used to evaluate the effects of various inhibitors on antibiotic susceptibility, while bioinformatic pipelines were used to characterize resistance determinants, virulence factors, and mobile genetic elements (MGEs).]]> Wed, 31 Dec 1969 19:00:00 EST Genomic and epigenomic insight into giga-chromosome architecture and adaptive evolution of royal lily (Lilium regale). Sun J, Wang X, Wang K, Meng D, Mu Y, Zhang L, Wang J, Yao G, Guo L
Nat Commun (Jul 2025)

Lilies are popular ornamental and medicinal plants with gigantic genomes. Due to the challenge of assembling complex giga-genomes, our understanding of the genetic architecture, epigenetic regulation and evolution of large-genome plants such as lily remains limited. Here, we report a high-quality chromosome-level 35.6 Gb reference genome of royal lily (Lilium regale), a parent of many modern lily cultivars, using PacBio HiFi and Hi-C sequencing data. We show that genome expansion of L. regale is mainly caused by extensive proliferation of transposable elements resulting in long intergenic and intronic regions, along with whole-genome duplications and tandem repeats. L. regale genome is repeat-rich (80.06%) encoding abundant large genes (>10 Kb) with long introns that account for ~90% length of 67,862 genes encoded. Phylogenomics reveals significant gene family expansion related to defense response and biosynthesis of terpenoids, reflecting its adaptation strategy. Through multiomic analysis, we reveal how transposable element activity and epigenetic regulations may impact transcription, alternative splicing, and three-dimensional organization, which contribute to its adaptive evolution. Collectively, this significantly improved lily genome assembly and annotation will serve as an essential resource for research on lily genetics, breeding, conservation biology, and angiosperm genome evolution.]]> Wed, 31 Dec 1969 19:00:00 EST Host-microbe multi-omics and succinotype profiling have prognostic value for future relapse in patients with inflammatory bowel disease. O'Sullivan J, Patel S, Leventhal GE, Fitzgerald RS, Laserna-Mendieta EJ, Huseyin CE, Konstantinidou N, Rutherford E, Lavelle A, Dabbagh K, DeSantis TZ, Shanahan F, Temko A, Iwai S, Claesson MJ
Gut Microbes (Dec 2025)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory bowel disorders (IBD), the pathogenesis of which is uncertain but includes genetic susceptibility factors, immune-mediated tissue injury and environmental influences, most of which appear to act via the gut microbiome. We hypothesized that host-microbe alterations could be used to prognostically stratify patients experiencing relapses up to four years after endoscopy. We therefore examined multiple omics data, including published and new datasets, generated from paired inflamed and non-inflamed mucosal biopsies from 142 patients with IBD (54 CD; 88 UC) and from 34 control (non-diseased) biopsies. The relapse-predictive potential of 16S rRNA gene and transcript amplicons (standing and active microbiota) were investigated along with host transcriptomics, epigenomics and genetics. While standard single-omics analysis could not distinguish between patients who relapsed and those that remained in remission within four years of colonoscopy, we did find an association between the number of flares and a patient's succinotype. Our multi-omics machine learning approach was also able to predict relapse when combining features from the microbiome and human host. Therefore multi-omics, rather than single omics, better predicts relapse within 4 years of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.]]> Wed, 31 Dec 1969 19:00:00 EST and are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Daskeviciute D, Sainty B, Chappell-Maor L, Bone C, Russell S, Iglesias-Platas I, Arnaud P, Monteagudo-Sánchez A, Greenberg MVC, Chen K, Manerao-Azua A, Perez de Nanclares G, Lartey J, Monk D
Epigenetics (Dec 2025)

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, and , both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.]]> Wed, 31 Dec 1969 19:00:00 EST Multigenerational exposure to DEHP drives dysregulation of imprinted gene Snurf to impair decidualization. Tan L, Gao R, Su Y, Zhang Y, Geng Y, Liu Q, Ma Y, Chen X, Li F, He J
J Hazard Mater (Aug 2025)

Phthalate-induced female reproductive health issues, particularly those related to di (2-ethylhexyl) phthalate (DEHP), are growing global concerns. Although most studies have focused on single-generation exposure, studies on prolonged DEHP exposure across multiple generations are limited. This study assessed the effects of multigenerational DEHP exposure on endometrial decidualization, which is crucial for embryo implantation. The results showed that sustained DEHP exposure over three generations exacerbated decidualization injury and led to adverse pregnancy outcomes. RNA sequencing revealed upregulation of the imprinted gene Snurf in the decidua, with changes that may not depend on alterations in DNA methylation. Knockdown of Snurf significantly alleviated in vitro decidualization deficiency induced by mono(2-ethylhexyl) phthalate (MEHP), the biologically active metabolite of DEHP. Proteomic analysis and the AlphaFold 3 algorithm indicated that Stn1 is a downstream target of Snurf, with silencing Stn1 resensitizing Snurf-knockdown stromal cells to MEHP. Human decidual stromal cells (hDSCs) from healthy participants showed sensitivity to MEHP, with the inhibition of decidualization. Epidemiological data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) indicated a positive association between DEHP exposure and female infertility. This study highlighted the cumulative toxic effects of multigenerational DEHP exposure on female reproduction and revealed the contribution of imprinted genes.]]> Wed, 31 Dec 1969 19:00:00 EST Mediators of maternal intergenerational epigenetic inheritance in mammals. Belton C, Kelsey G
Epigenomics (Jul 2025)

Experimental models and epidemiological data suggest that environmental factors, for example, adverse nutrition prior to conception, can lead to phenotypes in offspring of exposed parents in the absence of continued exposure. As a result these phenotypes have been described as epigentically inherited. The mechanistic basis for such phenomena has not been established in most cases. In this review, we consider possible contributing mechanisms for environmentaly induced epigenetic inheritance, with a focus on maternally transmitted effects and by comparing to paradigms of epigenetic inheritance with a clear mechanistic understanding. Genomic imprinting has provided an important conceptual framework for how the epigenetic states of parental germlines can determine allelic expression in offspring, yet, generally speaking, imprinted genes appear resilient to epigenetic disruption from altered parental environments. Metastable epialleles are environmentally sensitive and variably expressed loci that can impact organism phenotype, but the nature of any epigenetic marker at these loci transferred to offspring is unclear. Studies of examples across these forms of epigenetic inheritance show predominant effects are mediated by oocyte factors involved inreprogramming of the genome post-fertilization, rather than direct effects on gametic DNA methylation, with the exception of genomic imprinting. The potential contribution of additional oocyte chromatin features to the specific liability of phenotypic effector genes and their potential to persist through this reprogramming, however, remains to be investigated.]]> Wed, 31 Dec 1969 19:00:00 EST CT Biomarkers for Phenotypic Biological Aging: Emerging Concepts and Advantages. Lee MH, Garrett JW, Liu D, Pickhardt PJ
Radiographics (Aug 2025)

Aging is a complex phenomenon reflecting the time-dependent accumulation of damage that results in progressive structural and functional decline, disease risk, and death. Chronological age (CA) is an imperfect measure of health but remains an important driver of health care decisions. Biological age (BA) is a construct that attempts to provide a more holistic evaluation of the cumulative effects of aging and aging-related disease. The emergence of "omics"-based aging clocks (eg, epigenomics) has improved BA estimation, but imaging remains underutilized. CT biomarkers of muscle, fat, aortic calcification, and bone are examples of biomarkers of aging that can be used to construct a BA model (ie, CT-based biological age). As opposed to cellular and subcellular "frailomics" used in existing BA models, CT biomarkers are accessible and reproducible and reflect big-picture net phenotypic effects of aging at the tissue level (eg, using tissue segmentation). Recent technological advancements and improvements in artificial intelligence (AI) technologies have transformed our understanding of aging, and rapid automated AI tools enable scaling of image-based approaches for population-level impact. The understandable nature of explainable AI imaging tools instills trust in a model's prediction compared with opaque black box methodologies. Automated imaging-based body composition tools also can be applied opportunistically in either a retrospective or prospective fashion without the need for additional imaging, specialized testing, or patient time. Using a CT-based phenotypic approach to BA estimation is a practical example of opportunistic imaging that could be used to improve existing medical decision making and risk prediction for individual patient and societal benefit in ways that existing frailomics have failed. RSNA, 2025 See the invited commentary by Pyrros and Siddiqui in this issue.]]> Wed, 31 Dec 1969 19:00:00 EST Understanding the molecular basis of Sjögren's disease using omic technologies. Gómez-Gómez A, Aterido A, Li T, Guillén Y, Martínez S, Julià A, Marsal S, Andreu JL
Rheumatology (Oxford) (Jul 2025)

Primary Sjögren's Disease (SjD) is a chronic autoimmune disease (AD) that primarily affects the exocrine glands, particularly lacrimal and salivary glands, presenting extra glandular manifestations in a significant number of patients. Although it is a prevalent and globally widespread disease, its pathogenesis has not been fully elucidated. Recently, high-throughput omics technologies are providing unprecedented insights into the molecular landscape of various ADs, including SjD. These technical advances are prepared to decipher new aspects of its pathogenesis and to eventually enable the development of more effective treatment strategies. This review explores recent developments in genetics, transcriptomics, epigenomics, proteomics, and metagenomics in SjD, highlighting the potential of integrating multiple omics datasets to identify better drug targets and useful biomarkers for precision medicine.]]> Wed, 31 Dec 1969 19:00:00 EST A Possible More Precise Management Unit Delineation Based on Epigenomic Differentiation of a Long-Distance-Migratory Marine Fish Scomberomorus niphonius. Liu S, Gao Y, Long X, Li K, Gutang Q, Xie H, Wang J, Tian J, Liang B, Lin J, Liu W
Mol Ecol Resour (Aug 2025)

Understanding population structure and adaptive history is critical for designing appropriate management regulations for fisheries and conserving adaptive potential for the future. However, this is not easy for marine fish, especially those with long-distance migration abilities. In this study, we constructed a high-quality reference genome for Japanese Spanish mackerel (Scomberomorus niphonius) and explored its population structure using whole genomic and epigenomic data. Despite the high depth of the sequence data, we failed to identify geographical genetic differentiation of Japanese Spanish mackerel across Chinese coastal waters. However, whole-genome bisulphite sequencing can classify this species into the Bohai-Yellow Sea group and the East China Sea-South China Sea group. Genes involved in embryonic skeletal system development, limb morphogenesis functions, and adult locomotory behaviour were differentially methylated in the southern (Zhanjiang, ZJ) and northern (Western Dalian, WDL) populations and may play important roles as drivers of population structure in Japanese Spanish mackerel. Our study not only provides the first reference genome of the Japanese Spanish mackerel and sheds light on population differentiation at the epigenomic level, but also provides a methylome-based framework for population structure analyses of marine fish with long-distance migration ability. These findings are expected to facilitate the development of scientific programmes for the successful conservation of marine fishery resources.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-dimensional annotation of porcine variants using genomic and epigenomic features in pigs. Yin H, Yang L, Zhao Q, Yao W, Teng J, Gao Y, Xu Z, Lin Q, Diao S, Liu X, Zhao F, Zhou Z, Wang Q, Li J, Zhang Z, Zhou H, Groenen MAM, Madsen O, Bai L, Guan D, Fang L, Li K
BMC Biol (Jul 2025)

Investigating the functional impact of genomic variants is essential to uncover the molecular mechanisms behind complex traits. This study compiled a comprehensive dataset of 1,817 whole-genome sequences from diverse pig breeds and populations, capturing the global pig genetic diversity.]]> Wed, 31 Dec 1969 19:00:00 EST Fertile androgenetic mice generated by targeted epigenetic editing of imprinting control regions. Wei Y, Yue T, Wang Y, Yang Y
Proc Natl Acad Sci U S A (Jul 2025)

Each new mammalian life begins with the fusion of an oocyte and a sperm to produce a fertilized egg containing two sets of genomes, one from the mother and one from the father. Androgenesis, a way for producing offspring solely from male genetic material, is limited in mammals, presumably due to barriers arising from genomic imprinting, an epigenetic mechanism leading to monoallelic gene expression. Here, we report adult mammalian offspring derived from the genetic material of two sperm cells. These mice, which we refer to as androgenetic mice, were produced via targeted DNA methylation editing of seven imprinting control regions (ICRs) through CRISPR-based epigenome engineering. Two sperm cells were injected into an enucleated oocyte to form putatively diploid embryos. Allele-specific epigenetic editing was achieved by injecting guide RNAs with protospacer adjacent motif (PAM) sequences designed to match one allele but not the other. The birth of androgenetic mice that were able to develop to adulthood demonstrates that mammalian androgenesis is achievable by targeted epigenetic remodeling of a few defined ICRs.]]> Wed, 31 Dec 1969 19:00:00 EST Spatial profiling of chromatin accessibility in formalin-fixed paraffin-embedded tissues. Guo P, Chen Y, Mao L, Cardilla A, Lee CN, Cui Y, Jin D, Hua Y, Xu X, Deng Y
Nat Commun (Jul 2025)

Formalin-fixed paraffin-embedded (FFPE) samples represent a vast, untapped resource for epigenomic research, yet molecular tools for deep analysis of these specimens remain limited. We introduce spatial FFPE-ATAC-seq, an approach for in situ profiling chromatin accessibility within archived tissues. This approach overcomes formalin-induced crosslinking challenges, allowing high-resolution mapping of chromatin landscapes while preserving tissue architecture. Applying spatial FFPE-ATAC-seq to mouse and human tissues, including brain and thymus, reveals intricate spatial organization and distinct cell types in alignment with tissue morphology. Integration with single-cell RNA sequencing validates the precision of our chromatin profiles in identifying key cell types and regulatory elements. We further apply this method to human melanoma, comprehensively characterizing chromatin accessibility across both tumor and non-tumor regions. This method significantly expands the toolkit for epigenomic research, unlocking the potential of an extensive collection of archived FFPE samples for studying gene regulation and disease mechanisms with spatial context.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetics, human imprintome, and chronic diseases. Jirtle RL
Essays Biochem (Jul 2025)

Two epigenetically labile subsets of genes that link embryonic environmental exposures with adult disease susceptibility are those that are imprinted and those with metastable epialleles. The expression of genes with metastable epialleles, like the agouti gene in Agouti viable yellow (Avy) mice, is highly variable between individuals but uniform in tissues within an individual. We used the Avy mouse to demonstrate that exposure to nutritional supplements, chemical toxicants, and low-dose ionizing radiation during embryogenesis alters adult disease susceptibility by modifying the epigenome. Genomic imprinting is a unique species-dependent epigenetic form of gene regulation that evolved approximately 150 million years ago in a common ancestor to Therian mammals. It resulted in monoallelic parent-of-origin-dependent gene silencing. Thus, imprinted genes are functionally haploid disease susceptibility loci, since only a single genetic or epigenetic event is required to alter their function. Expression of imprinted genes in the human genome is regulated by hemi-methylated imprint control regions (ICRs) in the human imprintome. Furthermore, human imprintome ICRs associated with chronic diseases (e.g., cancer, diabetes, and obesity) and behavioral disorders (e.g., autism, bipolar disorder, psychopathy, and schizophrenia) can now be identified with the use of cells from peripheral samples and the human imprintome array. The importance of metastable epialleles and imprinted genes in the etiology of environmentally induced human chronic diseases is discussed in this review.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-omics analyses of the complex interplay between genetic variants, DNA methylation, and gene expression in COVID-19. Chen G, DeRoo L, Goodney G, Doumatey AP, Zhou J, Adeyemo AA, Rotimi CN, Gaye A
Am J Physiol Heart Circ Physiol (Jul 2025)

SARS-CoV-2, which drove the 2019 COVID-19 pandemic, continues to engender inquiries into the role of host genetic factors in disease susceptibility. Despite the identification of over 1,000 genes potentially associated with SARS-CoV-2 and COVID-19, the mechanisms connecting genetic variants to phenotype remain elusive. To shed light on these mechanisms, we undertook an integrated analysis, merging data from whole-genome association analyses of COVID-19 with methylome and transcriptomic. Study includes African American adults from the GENE-FORECAST study, encompassing 371 individuals with whole genome sequencing (WGS), 203 with DNA methylation, and 321 with RNA sequencing (RNA-Seq) of blood. 53.3% of participants reported COVID-19. Significant loci associated with COVID-19 were examined within the framework of methylation quantitative trait loci (mQTL) which located near the gene-of-original (-mQTL) and expression quantitative trait loci (eQTL) which located near the gene-of-origin (-eQTL), enabling analysis to assess mediators between genetic variants and COVID-19 status. Our analysis identified four intronic variants and confirmed a missense variant, rs1052067, in associated with COVID-19. Causal mediation analysis revealed that the combination of genetic variants within , epigenomics, and transcriptomics mapped four pathways influencing COVID-19 status. These pathways include: rs9659072 -> DNAm at chr1:156285845 (annotated to ) -> ENSG00000198715:13 (annotated to ); rs12083543 -> DNAm at chr1:155951748 () -> ENSG00000198715:13 (); rs1052067 -> DNAm at chr1:155951748 ()-> ENSG00000198715:13 (); rs1543294 -> ENSG00000198715:13 () -> DNAm at chr1:156077518 (). Through integrated multi-omics analyses, we identified genetic variants whose effects on COVID-19 susceptibility are mediated by changes in DNA methylation and mRNA expression. These findings offer insights into potential mechanistic pathways that merit further exploration.]]> Wed, 31 Dec 1969 19:00:00 EST