A methodology to identify a DNA methylation-based signature of prenatal air pollution exposure in the ECHO Cohort
Year: 2026
Type: article
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.
Source: Current Zoology
DOI: 10.1093/eep/dvag034
Authors: Abigail Gaylord, Julie D White, Tessa Bloomquist, Carrie Breton, Carlos A Camargo, Andres Cardenas, Elena Colicino, Dana Dabelea, Suman R Das, Rebecca C Fry, Jia Guo, Luhang Han, Christine W Hockett, Margaret R Karagas, Janine M LaSalle, Tengfei Ma, Amy Margolis, Grier Page, Frederica P Perera, Alicia K Peterson, Sima K Ramratnam, Annemarie Stroustrup, Rebecca J Schmidt, Jennifer K Straughen, Kristina W Whitworth, Shuang Wang, Julie B Herbstman
Institutions: Columbia University, RTI International, Washington University in St. Louis, Harvard University, Massachusetts General Hospital, Stanford University, University of Milan, Icahn School of Medicine at Mount Sinai, Colorado School of Public Health, Vanderbilt University Medical Center, University of North Carolina at Chapel Hill, University of Tennessee Health Science Center, University of South Dakota, Avera Health, Dartmouth College, University of California Davis Medical Center, University of California, Davis, Ball State University, Child Mind Institute, The Ohio State University, Kaiser Permanente, Kaiser Permanente Northern California, University of Wisconsin–Madison, Northwell Health, Cohen Children's Medical Center, Henry Ford Health + Michigan State University Health Sciences, Michigan State University, Baylor College of Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: Minnesota HHEAR Targeted Analysis Laboratory, G2766169687, Early Life Stress and the Environmental Origins of Disease: a Population-based Prospective Longitudinal Study of Children in Rural Poverty (ECHO), Wadsworth Center's Human Health and Exposure Analysis Resource (WC-HHEAR), Lifecourse Approach to Developmental Repercussions of Environmental Agents on Metabolic and Respiratory health (LA DREAMERs), Enriching ECHO Cohorts with High-risk Pregnancies and Children with Disabilities (Enriching ECHO), Developmental Impact of NICU Exposures (DINE), Breaking the cycle of intergenerational disadvantage: neurodevelopment among Puerto Rican children., Early Life Determinants of Child Health: A New Denver-Based Cohort, G9000042126, G9000043902, G9000119642, G9000182002, Early Life Exposure to Endocrine Disrupting Chemicals and Child Growth, Adiposity, and Neurodevelopment, Atlanta ECHO Pediatric Cohort, Host genetics, early-life microbiome, and childhood asthma: MARC-43 Boston, Environmental influences on Child Health Outcomes (ECHO) Coordinating Center, ASSESSING THE EVOLVING IMPACT OF EARLY LIFE EXPOSURES ON CHILD PHYSICAL HEALTH AND NEURODEVELOPMENT, Mount Sinai HHEAR Network Untargeted Lab Hub, Environmental influences on Child Health Outcomes in the Northern Plains PASS-ECHO Cohort, ECHO DAC (Environmental Influences on Child Health Outcomes Data Analysis Center), Wisconsin Infant Study Cohort (WISC) ECHO Pediatric Follow-Up, Human Health Exposure Analysis Resource (HHEAR): Coordinating Center, Mount Sinai HHEAR Network Targeted Lab Hub, ECHO-PROTECT Cohort Study Site in Puerto Rico, Environmental influences on Child Health Outcomes - The Colorado ECHO Pediatric Cohort, Human Health Exposure Analysis Resource (HHEAR) Data Center, The ECHO Measurement Core: A Framework and Resource for Assessing Environmental Exposure and Child Health, Duke Environmental Analysis Laboratory, ECHO Laboratory Core at Vanderbilt for Integrated Sample Biobanking and Processing
OpenAlex ID: W7221094371