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Environ Health Perspect. 2021 Sep;129(9):97008. doi: 10.1289/EHP8928. Epub 2021 Sep 13.

Epigenome-Wide DNA Methylation and Pesticide Use in the Agricultural Lung Health Study.

Environmental health perspectives

Thanh T Hoang, Cancan Qi, Kimberly C Paul, Mikyeong Lee, Julie D White, Marie Richards, Scott S Auerbach, Stuart Long, Srishti Shrestha, Tianyuan Wang, Laura E Beane Freeman, Jonathan N Hofmann, Christine Parks, Cheng-Jian Xu, Beate Ritz, Gerard H Koppelman, Stephanie J London

Affiliations

  1. Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA.
  2. Department of Pediatric Pulmonology and Pediatric Allergy, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, Netherlands.
  3. Groningen Research Institute for Asthma and Chronic Obstructive Pulmonary Disease, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
  4. Department of Epidemiology, University of California, Los Angeles Fielding School of Public Health, Los Angeles, California, USA.
  5. Westat, Durham, North Carolina, USA.
  6. Biomolecular Screening Branch, National Toxicology Program, NIEHS, NIH, DHHS, Morrisville, North Carolina, USA.
  7. Integrative Bioinformatics Support Group, NIH, DHHS, Research Triangle Park, North Carolina, USA.
  8. Occupational and Environmental Epidemiology Branch, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA.
  9. Research Group of Bioinformatics and Computational Genomics, CiiM, Centre for individualized infection medicine, a joint venture between Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  10. Department of Gastroenterology, Hepatology and Endocrinology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  11. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
  12. Department of Neurology, David Geffen School of Medicine, Los Angeles, California, USA.

PMID: 34516295 PMCID: PMC8437246 DOI: 10.1289/EHP8928

Abstract

BACKGROUND: Pesticide exposure is associated with many long-term health outcomes; the potential underlying mechanisms are not well established for most associations. Epigenetic modifications, such as DNA methylation, may contribute. Individual pesticides may be associated with specific DNA methylation patterns but no epigenome-wide association study (EWAS) has evaluated methylation in relation to individual pesticides.

OBJECTIVES: We conducted an EWAS of DNA methylation in relation to several pesticide active ingredients.

METHODS: The Agricultural Lung Health Study is a case-control study of asthma, nested within the Agricultural Health Study. We analyzed blood DNA methylation measured using Illumina's EPIC array in 1,170 male farmers of European ancestry. For pesticides still on the market at blood collection (2009-2013), we evaluated nine active ingredients for which at least 30 participants reported past and current (within the last 12 months) use, as well as seven banned organochlorines with at least 30 participants reporting past use. We used robust linear regression to compare methylation at individual C-phosphate-G sites (CpGs) among users of a specific pesticide to never users.

RESULTS: Using family-wise error rate (

DISCUSSION: We identified differential methylation for several active ingredients in male farmers of European ancestry. These may serve as biomarkers of chronic exposure and could inform mechanisms of long-term health outcomes from pesticide exposure. https://doi.org/10.1289/EHP8928.

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