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Peer-reviewedCC BY-NCEnvironmental epigenetics

A methodology to identify a DNA methylation-based signature of prenatal air pollution exposure in the ECHO Cohort.

15 more authors
29 affiliations
  1. 1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, United States.
  2. 2Genomics and Applied Public Health Center, RTI International, Research Triangle Park, NC 27713, United States.
  3. 3School of Public Health, Washington University in St. Louis, St. Louis, MO 63130, United States.
  4. 4Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, United States.
  5. 5Department of Epidemiology and Population Health, Stanford University, Stanford, CA 94305, United States.
  6. 6Department of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
  7. 7University of Milan, Milan, 20122, Italy.
  8. 8Department of Epidemiology, Colorado School of Public Health, Aurora, CO 13001, United States.
  9. 9Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
  10. 10Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, United States.
  11. 11Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, United States.
  12. 12Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, United States.
  13. 13Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
  14. 14Avera Research Institute, Sioux Falls, SD 57108, United States.
  15. 15Department of Pediatrics, School of Medicine, University of South Dakota, Sioux Falls, SD 57069, United States.
  16. 16Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, United States.
  17. 17Department of Medical Microbiology and Immunology, Genome Center, University of California Davis, Davis, CA 95616, United States.
  18. 18The MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, University of California Davis, Sacramento, CA 95817, United States.
  19. 19Department of Nutrition and Health Science, Ball State University, Muncie, IN 47306, United States.
  20. 20Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH 43210, United States.
  21. 21The Child Mind Institute, New York, NY 10022, United States.
  22. 22RTI International, Research Triangle Park, GA 27713, United States.
  23. 23Division of Research, Women's and Children's Health Section, Kaiser Permanente Northern California, Pleasanton, CA 94588, United States.
  24. 24Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 53792, United States.
  25. 25Division of Neonatology, Northwell Health Cohen Children's Medical Center, Hyde Park, NY 11042, United States.
  26. 26Department of Public Health Sciences, University of California Davis, Davis, CA 95616, United States.
  27. 27Henry Ford Health + Michigan State University Health Sciences, Detroit, MI 48202, United States.
  28. 28Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, 49503, United States.
  29. 29Department of Medicine, Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX 77030, United States.

Abstract

Prenatal exposure to ambient air pollutants has been associated with adverse child health across different populations. In the absence of direct air pollution exposure measures, epigenetic biomarkers can serve as indicators of cumulative exposure. Previously, we developed a methodological pipeline to build a prediction model to distinguish infants highly exposed to air pollutants in utero based on DNA methylation in cord blood samples. Here, we test and refine this pipeline using data from multiple pregnancy cohort sites included in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Levels of prenatal exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO₂), and 8-hour maximum ozone (O₃) were modeled using geocoded address data and machine learning. DNA methylation was measured using 450K or EPIC arrays. Training and validation sets were created and matched based on exposure level, cohort site, and array type to test the performance of the pipeline prediction model using area under the curve metrics. Among the three exposures, epigenetic-based predictions of PM2.5 and NO₂ produced higher area under the curve values (0.64-0.68 and 0.62-0.95, respectively) than those for O₃ (0.50-0.75). We identified differences in the performance of the pipeline model across geographical regions, exposure windows, and thresholds used to distinguish "high" and "low" air pollutant exposure. Overall, this pipeline enabled the estimation of air pollution from DNA methylation data, though careful consideration of model inputs is required. Further studies will test the performance of the CpG sites identified by the pipeline to predict child health outcomes.

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BibTeX
@article{gaylord2026methodology,
  title = {{A methodology to identify a DNA methylation-based signature of prenatal air pollution exposure in the ECHO Cohort.}},
  author = {Abigail Gaylord and Julie D White and Tessa Bloomquist and Carrie Breton and Carlos A Camargo and Andres Cardenas and Elena Colicino and Dana Dabelea and Suman R Das and Rebecca C Fry and Jia Guo and Luhang Han and Christine W Hockett and Margaret R Karagas and Janine M LaSalle and Tengfei Ma and Amy Margolis and Grier Page and Frederica P Perera and Alicia K Peterson and Sima K Ramratnam and Annemarie Stroustrup and Rebecca J Schmidt and Jennifer K Straughen and Kristina W Whitworth and Shuang Wang and Julie B Herbstman},
  journal = {Environmental epigenetics},
  year = {2026},
  month = oct,
  doi = {10.1093/eep/dvag034},
  url = {https://europepmc.org/article/MED/42959478},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - A methodology to identify a DNA methylation-based signature of prenatal air pollution exposure in the ECHO Cohort.
AU  - Abigail Gaylord
AU  - Julie D White
AU  - Tessa Bloomquist
AU  - Carrie Breton
AU  - Carlos A Camargo
AU  - Andres Cardenas
AU  - Elena Colicino
AU  - Dana Dabelea
AU  - Suman R Das
AU  - Rebecca C Fry
AU  - Jia Guo
AU  - Luhang Han
AU  - Christine W Hockett
AU  - Margaret R Karagas
AU  - Janine M LaSalle
AU  - Tengfei Ma
AU  - Amy Margolis
AU  - Grier Page
AU  - Frederica P Perera
AU  - Alicia K Peterson
AU  - Sima K Ramratnam
AU  - Annemarie Stroustrup
AU  - Rebecca J Schmidt
AU  - Jennifer K Straughen
AU  - Kristina W Whitworth
AU  - Shuang Wang
AU  - Julie B Herbstman
PY  - 2026
DA  - 2026/10/09
JO  - Environmental epigenetics
DO  - 10.1093/eep/dvag034
UR  - https://europepmc.org/article/MED/42959478
AB  - Prenatal exposure to ambient air pollutants has been associated with adverse child health across different populations. In the absence of direct air pollution exposure measures, epigenetic biomarkers can serve as indicators of cumulative exposure. Previously, we developed a methodological pipeline to build a prediction model to distinguish infants highly exposed to air pollutants in utero based on DNA methylation in cord blood samples. Here, we test and refine this pipeline using data from multiple pregnancy cohort sites included in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Levels of prenatal exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO₂), and 8-hour maximum ozone (O₃) were modeled using geocoded address data and machine learning. DNA methylation was measured using 450K or EPIC arrays. Training and validation sets were created and matched based on exposure level, cohort site, and array type to test the performance of the pipeline prediction model using area under the curve metrics. Among the three exposures, epigenetic-based predictions of PM2.5 and NO₂ produced higher area under the curve values (0.64-0.68 and 0.62-0.95, respectively) than those for O₃ (0.50-0.75). We identified differences in the performance of the pipeline model across geographical regions, exposure windows, and thresholds used to distinguish "high" and "low" air pollutant exposure. Overall, this pipeline enabled the estimation of air pollution from DNA methylation data, though careful consideration of model inputs is required. Further studies will test the performance of the CpG sites identified by the pipeline to predict child health outcomes.
SN  - 2058-5888
ER  -