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DNA Methylation Smoking Scores and Risk of Islet Autoimmunity and Type 1 Diabetes

Lauren A Vanderlinden1,2, Ellen Wong2, Randi K Johnson2,3

  • 1Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO.

Diabetes Care
|July 25, 2025
PubMed

Insights

Prenatal exposure to tobacco smoke, measured by maternal reports and DNA methylation, is linked to a lower risk of islet autoimmunity and type 1 diabetes in children. Further research is needed to understand these associations.

Area of Science:

  • Environmental Epigenetics
  • Autoimmune Disease Epidemiology
  • Pediatric Endocrinology

Background:

  • Previous studies suggest an inverse relationship between maternal smoking during pregnancy and offspring type 1 diabetes (T1D) risk.
  • Investigating objective biomarkers of smoke exposure, such as DNA methylation (DNAm) scores, is crucial for understanding this association.
  • Children at high risk for T1D provide a valuable cohort for studying early-life exposures and disease development.

Purpose of the Study:

  • To examine the association between DNAm-based smoke exposure scores and parental self-reported smoking with islet autoimmunity (IA) and T1D risk.
  • To validate DNAm scores as reliable proxies for in utero smoke exposure.
  • To assess the relationship between prenatal smoke exposure and T1D development in high-risk children.

Main Methods:

  • Longitudinal data from the Diabetes Autoimmunity Study in the Young cohort (205 IA cases, 206 controls) were analyzed.
  • DNA methylation profiles were assessed using Infinium Human Methylation 450K or EPIC BeadChips.
  • Three published DNAm smoking scores were calculated, and participant-specific intercepts from mixed-effects models served as proxies for in utero smoke exposure.

Main Results:

  • Both maternal self-reported smoking and higher DNAm smoking scores were inversely associated with IA and T1D risk.
  • Maternal smoking showed a significant inverse association with IA (OR 0.24).
  • DNAm smoking scores demonstrated consistent inverse associations with IA and T1D risk.

Conclusions:

  • The findings support existing literature linking in utero smoke exposure to reduced IA and T1D risk.
  • DNA methylation scores serve as valuable objective measures of prenatal smoke exposure.
  • Further investigation is warranted to elucidate the biological mechanisms underlying this protective association.
Abstract

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