DOP099 Tobacco Smoke Exposure from Prenatal to Adolescent Periods Drives IBD Pathogenesis: Dynamic DNA Methylation Signatures Across Lifespan Stages
Abstract
This study aims to comprehensively evaluate the association between early life exposure to smoking and the risk of inflammatory bowel disease (IBD), and to explore the role of DNA methylation in the effect of maternal smoking during pregnancy (MSDP) on IBD risk of offspring and whether common epigenetic pathways exist across different life stages.
We first conducted a prospective cohort study and meta-analysis to evaluate the association between smoking exposure from prenatal to adolescence periods and the IBD risk across lifespan stages. Leveraging available genome-wide association (GWAS, n = 59,957) and epigenome-wide association studies (EWAS, n = 161∼6,685), an epigenetic Mendelian randomization (MR) study was then conducted to characterize dynamic DNA methylation signatures associated with early-life smoke exposure and their effect on IBD pathogenesis. External EWAS of IBD, colocalization analysis, and gene expression and single cell sequencing analyses in colorectal tissues were interrogated to validate epigenetic signals. Finally, we explored common DNA methylation pathways involved in the effects of smoking exposure on IBD across different life stages.
With a median follow-up of 13·9 years, the observational study in UK Biobank cohort demonstrated that MSDP was associated with increased risk of IBD (HR = 1·13, 95%CI: 1·05-1·22), CD (HR = 1·21, 95%CI: 1·05-1·39), and UC (HR = 1·11, 95%CI: 1·01-1·23) in offspring. Individuals who started smoking in adolescence had a…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 59,957 participants or records.
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