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

Details

• Personal Author:
  Auerbach SS ; Beane Freeman LE ; BIOS Consortium ; Hoang TT ; Hofmann JN ; Koppelman GH ; Lee M ; London SJ ; Long S ; Parks C ; Paul KC ; Qi C ; Richards M ; Ritz B ; Shrestha S ; Wang T ; White JD ; Xu C-J
• Description:
  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 (p<9×10-8) or false-discovery rate (0.05FDR<0.05), we identified 162 differentially methylated CpGs across 8 of 9 currently marketed active ingredients (acetochlor, atrazine, dicamba, glyphosate, malathion, metolachlor, mesotrione, and picloram) and one banned organochlorine (heptachlor). Differentially methylated CpGs were unique to each active ingredient, and a dose-response relationship with lifetime days of use was observed for most. Significant CpGs were enriched for transcription motifs and 28% of CpGs were associated with whole blood cis-gene expression, supporting functional effects of findings. We corroborated a previously reported association between dichlorodiphenyltrichloroethane (banned in the United States in 1972) and epigenetic age acceleration. 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. [Description provided by NIOSH]
• Subjects:
  Agriculture Biomarkers Epidemiology Farmers Insecticides Occupational Exposure Occupational Health Safety
• Keywords:
  Agricultural Workers Chronic Exposure DNA Damage Gene Expression Genetic Factors Pesticides
• ISSN:
  0091-6765
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Maryland ; North Carolina ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  129
• Issue:
  9
• NIOSHTIC Number:
  nn:20068239
• Citation:
  Environ Health Perspect 2021 Sep; 129(9):97008
• Contact Point Address:
  Stephanie J. London, National Institute of Environmental Health Sciences, P.O. Box 12233, MD A3-05, Research Triangle Park, NC 27709 USA
• Email:
  london2@niehs.nih.gov
• Federal Fiscal Year:
  2021
• Performing Organization:
  University of California Los Angeles
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Environmental Health Perspectives
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c55ec443f54cb0ec94d4b888053c6180fa4446681d66ddd3aeef2d8f968ac6a180dc17e3aaed810b59cf4b7ea2f48cfe32598d8149a5755002dcc9c33d2cceaf
• Download URL:
  https://stacks.cdc.gov/view/cdc/230440/cdc_230440_DS1.pdf
• File Type:
  [PDF - 164.10 KB ]