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Published on: September 18, 2020
Systematic Review and Meta-analysis of Peripheral Blood DNA Methylation Studies in Inflammatory Bowel Disease
Vincent Joustra1,2, Ishtu L Hageman1,2,3, Jack Satsangi4
1Amsterdam UMC location University of Amsterdam, Department of Gastroenterology and Hepatology, Meibergdreef 9, Amsterdam, Netherlands.
Background And Aims:
Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary and meta-analysis of peripheral blood leukocyte [PBL] DNA methylation studies has thus far not been conducted. Here, we systematically reviewed all available literature up to February 2022 and summarized the observations by means of meta-analysis.
Methods:
We conducted a systematic search and critical appraisal of IBD-associated DNA methylation studies in PBL using the biomarker-based cross-sectional studies [BIOCROSS] tool. Subsequently, we performed meta-analyses on the summary statistics obtained from epigenome-wide association studies [EWAS] that included patients with Crohn's disease [CD], ulcerative colitis [UC] and/or healthy controls [HC].
Results:
Altogether, we included 15 studies for systematic review. Critical appraisal revealed large methodological and outcome heterogeneity between studies. Summary statistics were obtained from four studies based on a cumulative 552 samples [177 CD, 132 UC and 243 HC]. Consistent differential methylation was identified for 256 differentially methylated probes [DMPs; Bonferroni-adjusted p ≤ 0.05] when comparing CD with HC and 103 when comparing UC with HC. Comparing IBD [CD + UC] with HC resulted in 224 DMPs. Importantly, several of the previously identified DMPs, such as VMP1/TMEM49/MIR21 and RPS6KA2, were consistently differentially methylated across all studies.
Conclusion:
Methodological homogenization of IBD epigenetic studies is needed to allow for easier aggregation and independent validation. Nonetheless, we were able to confirm previous observations. Our results can serve as the basis for future IBD epigenetic biomarker research in PBL.
Insights
This meta-analysis summarizes DNA methylation patterns in peripheral blood leukocytes of inflammatory bowel disease patients. It confirms previously identified epigenetic markers, providing a foundation for future biomarker research in Crohn's disease and ulcerative colitis.
Area of Science:
- Epigenetics
- Genomics
- Immunology
Background:
- Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is increasingly studied at the DNA methylome level in peripheral blood.
- A comprehensive meta-analysis of peripheral blood leukocyte (PBL) DNA methylation studies in IBD patients has been lacking.
Approach:
- Systematic literature review and critical appraisal of IBD-associated DNA methylation studies in PBL up to February 2022.
- Meta-analysis of summary statistics from epigenome-wide association studies (EWAS) comparing CD, UC, and/or healthy controls (HC).
- Utilized the biomarker-based cross-sectional studies (BIOCROSS) tool for study appraisal.
Key Points:
- Fifteen studies were included in the systematic review, revealing significant methodological and outcome heterogeneity.
- Meta-analysis of four studies (552 samples) identified 256 differentially methylated probes (DMPs) in CD vs. HC and 103 DMPs in UC vs. HC.
- Consistent differential methylation was observed for specific DMPs, including VMP1/TMEM49/MIR21 and RPS6KA2, across studies.
Conclusions:
- Methodological standardization in IBD epigenetic studies is crucial for data aggregation and validation.
- The study confirms previously reported epigenetic alterations in IBD patients' PBL.
- Findings provide a basis for future epigenetic biomarker discovery in IBD.
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