ArticleInflammatory bowel diseases2014
Two-stage genome-wide methylation profiling in childhood-onset Crohn's Disease implicates epigenetic alterations at the VMP1/MIR21 and HLA loci.
Article in Inflammatory bowel diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Systematic Review and Meta-analysis of Peripheral Blood DNA Methylation Studies in Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2023Pooled it
- From signals to systems: the epigenetic-microbiome-mitochondrial axis in IBD pathogenesis.Gut microbes · 2026Review
- Epigenetic biomarkers in inflammatory bowel diseases-computational challenges and opportunities.Journal of Crohn's & colitis · 2026Review
- Article
- Article
- The Circulating Methylome in Childhood-Onset Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2025Article
- SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model.Cell death discovery · 2025Article
- Epigenetic age acceleration and methylation differences in IgG4-related cholangitis and primary sclerosing cholangitis.Clinical epigenetics · 2025Article
- Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.Epigenetics · 2024Article
- Stability of Blood DNA Methylation Across Two Timepoints in Three Cohorts.Biomedicines · 2024Article
- Peripheral Blood DNA Methylation Signatures and Response to Tofacitinib in Moderate-to-severe Ulcerative Colitis.Journal of Crohn's & colitis · 2024Article
- Exploring regulatory mechanisms on miRNAs and their implications in inflammation-related diseases.Clinical and experimental medicine · 2024Review
- An isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn's disease with defective antimicrobial activity.Nature communications · 2024Article
- Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease.Clinical epigenetics · 2024Article
- Article
- Are We Ready to Reclassify Crohn's Disease Using Molecular Classification?Journal of clinical medicine · 2023Article
- Transcriptomic Context ofBiomedicines · 2023Article
- Review
- Analysis of Systemic Epigenetic Alterations in Inflammatory Bowel Disease: Defining Geographical, Genetic and Immune-Inflammatory influences on the Circulating Methylome.Journal of Crohn's & colitis · 2023Article
- Mucosal DNA methylome alteration in Crohn's disease: surgical and non-surgical groups.Frontiers in genetics · 2023Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundAs a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohn's disease (CD) and is especially pertinent to early onset disease.
methodsThe Illumina 450K platform was applied to assess epigenome-wide methylation profiles in circulating leukocyte DNA in discovery and replication pediatric CD cohorts and controls. Data were corrected for differential leukocyte proportions. Targeted replication was performed in adults using pyrosequencing. Methylation changes were correlated with gene expression in blood and intestinal mucosa.
resultsWe identified 65 individual CpG sites with methylation alterations achieving epigenome-wide significance after Bonferroni correction (P < 1.1 × 10(-7)), and 19 differently methylated regions displaying unidirectional methylation change. There was a highly significant enrichment of methylation changes around GWAS single nucleotide polymorphisms (P = 3.7 × 10(-7)), notably the HLA region and MIR21. Two-locus discriminant analysis in the discovery cohort predicted disease in the pediatric replication cohort with high accuracy (area under the curve, 0.98). The findings strongly implicate the transcriptional start site of MIR21 as a region of extended epigenetic alteration, containing the most significant individual probes (P = 1.97 × 10(-15)) within a GWAS risk locus. In extension studies, we confirmed hypomethylation of MIR21 in adults (P = 6.6 × 10(-5), n = 172) and show increased mRNA expression in leukocytes (P < 0.005, n = 66) and in the inflamed intestine (P = 1.4 × 10(-6), n = 99).
conclusionsWe demonstrate highly significant and replicable differences in DNA methylation in CD, defining the disease-associated epigenome. The data strongly implicate known GWAS loci, with compelling evidence implicating MIR21 and the HLA region.
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