Epigenome-wide Association Study of DNA Methylation and Specific Pesticide Use Among U.S. Farmers

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Background: Pesticide exposure is associated with certain cancers and neurologic diseases, but the underlying mechanisms are not fully understood. DNA methylation, an epigenetic modification, may play a role. DNA methylation patterns likely differ by specific pesticide, but no epigenome-wide association studies have evaluated methylation patterns across different pesticides. We conducted epigenome-wide analyses of DNA methylation in relation to several pesticides used among U.S. farmers.Methods: The Agricultural Lung Health Study (ALHS) is a case-control study of asthma, nested within the Agricultural Health Study (AHS). For 1,170 ALHS male farmers, blood DNA methylation was measured with Illumina’s MethylationEPIC array. Participants self-reported pesticide use in the AHS (past use) and ALHS (current use, defined as past 12 months). Pesticides were grouped by chemical class and active ingredients. Using robust linear regression, we analyzed 13 chemical classes and 16 active ingredients with 30+ exposed men. Analyses were adjusted for age, smoking status, packyears, state, asthma status, and estimated cell type proportions.Results: Participants who reported past and current use of pesticide class or active ingredient were compared to those who never reported use. Using family-wise error rate (p<9×10-8) or false discovery rate (p<0.05), we identified differentially methylated C-phosphate-G (CpG) sites for 10 chemical classes and 9 active ingredients. Most differentially methylated CpG sites were unique to each active ingredient. For 5 of the 9 active ingredients, lifetime days of use was available and there was evidence of a dose-response at most differentially methylated CpG sites. Significant CpG sites were enriched for transcription factor motifs. We plan to correlate significant CpG sites with gene expression in external data.Conclusions: We observed differential methylation associated with several chemical classes and active ingredients. These differential methylation patterns could be biomarkers of long-term exposure and may provide additional biological insight into health effects of pesticide exposure.

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