Journal of Crohn's & colitis · 2025
The Circulating Methylome in Childhood-Onset Inflammatory Bowel Disease.
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Noble Alexandra, Adams Alex, Nowak Jan, Cheng Guo, Nayak Komal, Quinn Aisling, Kristiansen Mark, Kalla Rahul, Ventham Nicholas T, Giachero Federica, Jayamanne Chamara, Hansen Richard, Hold Georgina L, El-Omar Emad, Croft Nicholas M, Wilson David, Beattie R Mark, Ashton James J, Zilbauer Matthias, Ennis Sarah, Uhlig Holm H, Satsangi Jack
Аннотация
BACKGROUND: The genetic contribution to inflammatory bowel disease (IBD), encompassing both Crohn's disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterize environmental and epigenetic influences. Recently, considerable progress has been made in characterizing the adult methylome in epigenome-wide association studies.
METHODS: We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD and UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform.
RESULTS: We derived and validated a 4-probe methylation biomarker (RPS6KA2, VMP1, CFI, and ARHGEF3), with specificity and high diagnostic accuracy for pediatric IBD in UK and North American cohorts (area under the curve: 0.90-0.94). Significant epigenetic age acceleration is present at diagnosis, with the greatest observed in CD patients. Cis-methylation quantitative trait loci (meQTL) analysis identifies genetic determinants underlying epigenetic alterations notably within the HLA 6p22.1-p21.33 region. Passive smoking exposure is associated with the development of UC rather than CD, contrary to previous findings.
CONCLUSIONS: These data provide new insights into epigenetic alterations in IBD and illustrate the reproducibility and translational potential of epigenome-wide association studies in complex diseases.
METHODS: We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD and UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform.
RESULTS: We derived and validated a 4-probe methylation biomarker (RPS6KA2, VMP1, CFI, and ARHGEF3), with specificity and high diagnostic accuracy for pediatric IBD in UK and North American cohorts (area under the curve: 0.90-0.94). Significant epigenetic age acceleration is present at diagnosis, with the greatest observed in CD patients. Cis-methylation quantitative trait loci (meQTL) analysis identifies genetic determinants underlying epigenetic alterations notably within the HLA 6p22.1-p21.33 region. Passive smoking exposure is associated with the development of UC rather than CD, contrary to previous findings.
CONCLUSIONS: These data provide new insights into epigenetic alterations in IBD and illustrate the reproducibility and translational potential of epigenome-wide association studies in complex diseases.