An epigenome-wide association study of ambient pyrethroid pesticide exposures in California's central valley

Furlong, Melissa; Paul, Kimberly C.; Yan, Qi; Chuang, Yen; Cockburn, Myles; Bronstein, Jeff M.; Horvath, Steve; Ritz, Beate

doi:10.1016/j.ijheh.2020.113569

Cited by 22 publications

(26 citation statements)

References 101 publications

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“…The PEG Study previously reported differentially methylated CpGs in relation to organophosphate, 70 CpGs at

(

) ( Paul et al. 2018 ), and pyrethroid, 4 CpGs at

( Furlong et al. 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Future development of mixtures methods and convenient code suitable for epigenome-wide analysis would be of interest. Thus, although we did not conduct a mixtures analysis, we attempted to replicate (

in the ALHS and the same direction of association) the differentially methylated CpGs that the PEG Study previously reported to be associated with organophosphate and pyrethroid, two common pesticide classes ( Furlong et al. 2020 ; Paul et al.…”

Section: Discussionmentioning

confidence: 99%

“…The PEG Study previously reported 70 CpGs associated with organophosphates ( Paul et al. 2018 ) at

(

) and four differentially methylated CpGs associated with pyrethroids at

( Furlong et al. 2020 ).…”

Section: Methodsmentioning

confidence: 99%

“…Differential methylation was reported in relation to the two pesticide classes, organophosphates ( Paul et al. 2018 ) and pyrethroids ( Furlong et al. 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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

Hoang

Paul

et al. 2021

Environ Health Perspect

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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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“…The PEG Study previously reported differentially methylated CpGs in relation to organophosphate, 70 CpGs at

(

) ( Paul et al. 2018 ), and pyrethroid, 4 CpGs at

( Furlong et al. 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The PEG Study previously reported 70 CpGs associated with organophosphates ( Paul et al. 2018 ) at

(

) and four differentially methylated CpGs associated with pyrethroids at

( Furlong et al. 2020 ).…”

Section: Methodsmentioning

confidence: 99%

“…Differential methylation was reported in relation to the two pesticide classes, organophosphates ( Paul et al. 2018 ) and pyrethroids ( Furlong et al. 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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

Hoang

Paul

et al. 2021

Environ Health Perspect

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“… 6 , 23 – 25 We additionally previously reported that pyrethroid exposures were associated with changes in epigenetic pathways that are consistent with depression and alterations in mood. 26 …”

Section: Discussionmentioning

confidence: 99%

Ambient Pyrethroid Pesticide Exposures in Adult Life and Depression in Older Residents of California’s Central Valley

Furlong

Paul

Cockburn

et al. 2020

Environmental Epidemiology

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Pyrethroid pesticide exposures may be associated with the onset of depression in later life via disruption of dopaminergic, serotonergic, and neurological functioning. We sought to investigate the association between living near agricultural pyrethroid pesticide applications and depression measures in central California, using two waves (PEG 1&2, total N = 1,654) of a case control study of Parkinson’s disease (PD). At enrollment, participants self-reported history of use of depression medications and dates of MD-diagnosed depression and anxiety. Participants also completed a Geriatric Depression Scale-Short Form upon enrollment. We used the California Pesticide Use Registry to assign estimated ambient pyrethroid pesticide exposures at participant’s home addresses over the 5 years before the index date (date of outcome, or an age-matched year for participants without the outcome). We used logistic and linear regression to evaluate associations between living near any pyrethroid applications over the 5-year index period and measures of depression and anxiety. We also evaluated modification by study wave and PD status. We observed associations of pyrethroids with depression, depression medications, and anxiety (adjusted odds ratio [aOR] depression = 1.54, 95% confidence interval [CI] 1.14, 2.07; aOR depression medications = 1.68, 95% CI 1.25, 2.25; aOR anxiety = 1.60, 95% CI 1.17, 2.18). However, we observed no associations with mild/moderate depressive symptoms according to the GDS score at enrollment (aOR = 1.04, 95% CI 0.77, 1.42). We did not observe a consistent modification of the pyrethroid-depression associations by study wave and PD status. Ambient pyrethroid pesticide exposures may be associated with measures of depression in later life.

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Epigenetic effects of parasites and pesticides on captive and wild nestling birds

McNew

Boquete

Espinoza-Ulloa

et al. 2021

Ecology and Evolution

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An epigenome-wide association study of ambient pyrethroid pesticide exposures in California's central valley

Cited by 22 publications

References 101 publications

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

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

Ambient Pyrethroid Pesticide Exposures in Adult Life and Depression in Older Residents of California’s Central Valley

Epigenetic effects of parasites and pesticides on captive and wild nestling birds

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