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

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 ( ) or false-discovery rate ( ), 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. https://doi.org/10.1289/EHP8928

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“… 35 Inflated test statistics (lambda) was corrected using BACON, and p -values were estimated after correction for inflation and bias in the study. Previous studies of epigenome-wide analyses of DNA methylation using BACON package reported lambda varying from 0.79 to 1.40, 36 , 37 which supported the confidence of our study (lambda:1.29). A false discovery rate (FDR) threshold was determined at and delta beta was determined at as the threshold for epigenome-wide testing.…”

Current status of pesticide effects on environment, human health and it’s eco-friendly management as bioremediation: A comprehensive review

“…Such genetic modifications could act as carcinogenic agents. Differentially methylated CpGs have been found to be unique to the active ingredients of marketed pesticides such as mesotrione, dicamba, acetochlor, picloram atrazine, malathion, glyphosate, and metolachlor ( Hoang et al, 2021 ). Occupational and non-occupational pesticide exposure, as well as chronic and high pesticide exposure in human beings, lead to altered genomic methylation.…”

Bioreactivity of a novel poly(epsilon-caprolactone) nanocapsule containing atrazine with human lung alveolar epithelial cells

“…40 A recent finding of the AHS, in a genome-wide DNA methylation study, found methylation of PAX6 with ATZ; this implicates ATZ exposure in the development of diabetes and abnormal eye development. 41 The United States Geological Survey reported ten or more pesticide contaminants in approximately 20% of their tests and two or more in 90% of their tests in streams. 42 Thus, flora and fauna are consistently exposed to multiple pesticides and, indeed, large quantities of ATZ are lost to the environment.…”

“…40 A recent finding of the AHS, in a genome-wide DNA methylation study, found methylation of PAX6 with ATZ; this implicates ATZ exposure in the development of diabetes and abnormal eye development. 41…”