ArticleEpigenetics2019
Epigenomic profiling of newborns with isolated orofacial clefts reveals widespread DNA methylation changes and implicates metastable epiallele regions in disease risk.
Article in Epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.Molecular genetics and genomics : MGG · 2026Article
- Epigenetic Signatures in Monozygotic and Dizygotic Twins Discordant for Orofacial Clefts.medRxiv : the preprint server for health sciences · 2026Article
- DNA methylation as a biomarker of prenatal exposures: current challenges and opportunities.Environmental epigenetics · 2026Review
- Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.medRxiv : the preprint server for health sciences · 2025Article
- Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.International journal of molecular sciences · 2025Review
- Cleft Palate Induced by Mycophenolate Mofetil Is Associated withNon-coding RNA · 2025Article
- Non-coding 886 (Epigenetics · 2024Review
- Disruption of DNA methylation-mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ezh2-dependent methylation in oral epithelia promotes secondary palatogenesis.Birth defects research · 2023Article
- Sex differences in childhood cancer risk among children with major birth defects: a Nordic population-based nested case-control study.International journal of epidemiology · 2023Article
- The impact of developmental genes in non-syndromic cleft lip and/or palateJournal of the Turkish German Gynecological Association · 2023Article
- MicroRNAs and Gene Regulatory Networks Related to Cleft Lip and Palate.International journal of molecular sciences · 2023Review
- Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control.Genome biology · 2023Article
- Gene-environment interactions in birth defect etiology: Challenges and opportunities.Current topics in developmental biology · 2023Review
- DNA methylation differences in monozygotic twins with Van der Woude syndrome.Frontiers in dental medicine · 2023Article
- mEpigenetics · 2022Article
- Alterations in DNA Methylation in Orofacial Clefts.International journal of molecular sciences · 2022Review
- Vitamin B12 Transport Genes and Nonsyndromic Cleft Lip With or Without Cleft Palate in Chile.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Epigenetic Effect of Maternal Methyl-Group Donor Intake on Offspring's Health and Disease.Life (Basel, Switzerland) · 2022Review
- Methylation pattern of polymorphically imprinted nc886 is not conserved across mammalia.PloS one · 2022Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
Cleft lip with or without cleft palate (CL/P) is a common human birth defect whose etiologies remain largely unknown. Several studies have demonstrated that periconceptional supplementation of folic acid can reduce risk of CL/P in offspring. In this study, we tested the hypothesis that the preventive effect of folic acid is manifested through epigenetic modifications by determining whether DNA methylation changes are associated with CL/P. To more readily observe the potential effects of maternal folate on the offspring epigenome, we focused on births prior to mandatory dietary folate fortification in the United States (i.e. birth year 1997 or earlier). Genomic DNA methylation levels were assessed from archived newborn bloodspots in a 182-member case-control study using the Illumina® Human Beadchip 450K array. CL/P cases displayed striking epigenome-wide hypomethylation relative to controls: 63% of CpGs interrogated had lower methylation levels in case newborns, a trend which held up in racially stratified sub-groups. 28 CpG sites reached epigenome-wide significance and all were case-hypomethylated. The most significant CL/P-associated differentially methylated region encompassed the VTRNA2-1 gene, which was also hypomethylated in cases (FWER p = 0.014). This region has been previously characterized as a nutritionally-responsive, metastable epiallele and CL/P-associated methylation changes, in general, were greater at or near putative metastable epiallelic regions. Gene Set Enrichment Analysis of CL/P-associated DMRs showed an over-representation of genes involved in palate development such as WNT9B, MIR140 and LHX8. CL/P-associated DNA methylation changes may partly explain the mechanism by which orofacial clefts are responsive to maternal folate levels.
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