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Genetic influences on DNA methylation (mQTL) in pediatric Crohn's disease patients

ABSTRACT: Genetic influences on DNA methylation (mQTL) in pediatric Crohn's disease patients

PROVIDER: PRJNA560536 | ENA |

REPOSITORIES: ENA

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Genetic influences on DNA methylation (mQTL) in pediatric Crohn's disease patients

Project description:Previously, we conducted an epigenome-wide study of DNA methylation (~850K sites) in peripheral blood at diagnosis and during follow-up from the RISK pediatric Crohn’s disease inception cohort and data are deposited in GEO with an access number GSE112611. We further followed up this study and identified here the genetic influence on ~850K DNAm sites (mQTL) in peripheral blood as well as newly added 41 ileal biopsies. All the ileal biopsies DNAm data are collected from the subset of primary 238 pediatric CD cohort that contains the peripheral blood DNAm data in GSE112611. Comparing the mQTL effect sizes among 164 CD cases at baseline, 164 CD cases at 3 years follow-up, 74 healthy controls and 41 ileal biopsies confirms that genetic influence on DNAm sites are strongly consistent among these groups. This study further concludes that the mQTLs are largely not disease-specific or inflammation-specific or tissue-specific.

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Transcriptomic profile of intestinal epithelial cells obtained from ileal endoscopic biopsies from newly-diagnosed, pediatric Crohn's disease patients and healthy controls.

Project description:Purpose: To uncover differentially-regulated transcripts and pathways/biological processes in newly-diagnosed, pediatric Crohn's disease in comparison to healthy controls. Methods: Intestinal epithelial cells were dissociated from ileal endoscopic biopsies, and stored at -80C in RNAlater. The polyA RNA fraction was purified, and single-end, 50 bp reads were sequenced and aligned to the Hg19 genome using the TopHat2 aligner. Differential analysis was performed using Bioconductor packages including edgeR, where significance was defined as p<0.05 and fold change>2. Results: We obtained 15788 reasonably-expressed transcripts that were included in differential analyses. Conclusions: Our study characterizes the dysregulation of intestinal epithelial cells in treatment-naïve Crohn's disease using RNA sequencing for transcriptomic profile of cells obtained through ileal endoscopic biopsies.

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Project description:Comparison of gene expression from ileal biopsies of Crohn's Disease patients and non-IBD controls

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Project description:The aim of the present study was to identify a pediatric inflamatory bowel disease (pIBD) characteristic microRNA profile serving as potential Crohns disease and ulcerative colitis specific diagnostic pattern and to further analyze the related target genes. Illumina small RNA sequencing was performed on inflamed and intact colonic biopsies of Crohn's disease and control patients. Selected miRs were further investigated by real-time reverse transcription (RT)-PCR. To analyze network connection of differentially expressed miRs and their target genes the MiRTarBase database and previous transcriptome sequencing data were used. We demonstrated a characteristic colonic miR pattern in pIBD that could facilitate deeper understanding of the pathomechanism of IBD and may serve as a diagnostic tool in the future.

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