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

doi:10.1289/EHP8928

. 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

Thanh T Hoang¹, Cancan Qi^{2

3}, Kimberly C Paul⁴, Mikyeong Lee¹, Julie D White¹, Marie Richards⁵, Scott S Auerbach⁶, Stuart Long⁵, Srishti Shrestha¹, Tianyuan Wang⁷, Laura E Beane Freeman⁸, Jonathan N Hofmann⁸, Christine Parks¹; BIOS Consortium; Cheng-Jian Xu^{9

10

11}, Beate Ritz^{4

12}, Gerard H Koppelman^{2

3}, Stephanie J London¹

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

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

Thanh T Hoang et al. Environ Health Perspect. 2021 Sep.

. 2021 Sep;129(9):97008.

doi: 10.1289/EHP8928. Epub 2021 Sep 13.

Authors

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 ( $p < 9 \times 10^{- 8}$ ) or false-discovery rate ( $FDR < 0.05$ ), 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. https://doi.org/10.1289/EHP8928.

PubMed Disclaimer

Cited by

Linking Prenatal Environmental Exposures to Lifetime Health with Epigenome-Wide Association Studies: State-of-the-Science Review and Future Recommendations.
Bakulski KM, Blostein F, London SJ. Bakulski KM, et al. Environ Health Perspect. 2023 Dec;131(12):126001. doi: 10.1289/EHP12956. Epub 2023 Dec 4. Environ Health Perspect. 2023. PMID: 38048101 Free PMC article. Review.
Association analysis between an epigenetic alcohol risk score and blood pressure.
Bui H, Keshawarz A, Wang M, Lee M, Ratliff SM, Lin L, Birditt KS, Faul JD, Peters A, Gieger C, Delerue T, Kardia SLR, Zhao W, Guo X, Yao J, Rotter JI, Li Y, Liu X, Liu D, Tavares JF, Pehlivan G, Breteler MMB, Karabegovic I, Ochoa-Rosales C, Voortman T, Ghanbari M, van Meurs JBJ, Nasr MK, Dörr M, Grabe HJ, London SJ, Teumer A, Waldenberger M, Weir DR, Smith JA, Levy D, Ma J, Liu C. Bui H, et al. Clin Epigenetics. 2024 Oct 28;16(1):149. doi: 10.1186/s13148-024-01753-4. Clin Epigenetics. 2024. PMID: 39468603 Free PMC article.
Association analysis between an epigenetic risk score and blood pressure.
Bui H, Keshawarz A, Wang M, Lee M, Ratliff SM, Lin L, Birditt KS, Faul JD, Peters A, Gieger C, Delerue T, Kardia SLR, Zhao W, Guo X, Yao J, Rotter JI, Li Y, Liu X, Liu D, Tavares JF, Pehlivan G, Breteler MMB, Karabegovic I, Ochoa-Rosales C, Voortman T, Ghanbari M, van Meurs JBJ, Nasr MK, Dörr M, Grabe HJ, London SJ, Teumer A, Waldenberger M, Weir DR, Smith JA, Levy D, Ma J, Liu C. Bui H, et al. Res Sq [Preprint]. 2024 Apr 19:rs.3.rs-4243866. doi: 10.21203/rs.3.rs-4243866/v1. Res Sq. 2024. Update in: Clin Epigenetics. 2024 Oct 28;16(1):149. doi: 10.1186/s13148-024-01753-4. PMID: 38699335 Free PMC article. Updated. Preprint.
Exposure to Pesticides and Breast Cancer in an Agricultural Region in Brazil.
Panis C, Candiotto LZP, Gaboardi SC, Teixeira GT, Alves FM, da Silva JC, Scandolara TB, Rech D, Gurzenda S, Ponmattam J, Ohm J, Castro MC, Lemos B. Panis C, et al. Environ Sci Technol. 2024 Jun 18;58(24):10470-10481. doi: 10.1021/acs.est.3c08695. Epub 2024 Jun 6. Environ Sci Technol. 2024. PMID: 38844831 Free PMC article.
Pesticide use and risk of systemic autoimmune diseases in the Agricultural Health Study.
Parks CG, Costenbader KH, Long S, Hofmann JN, Beane FLE, Sandler DP. Parks CG, et al. Environ Res. 2022 Jun;209:112862. doi: 10.1016/j.envres.2022.112862. Epub 2022 Feb 4. Environ Res. 2022. PMID: 35123967 Free PMC article.

See all "Cited by" articles

References

1. Alavanja MC, Sandler DP, McMaster SB, Zahm SH, McDonnell CJ, Lynch CF, et al. . 1996. The Agricultural Health Study. Environ Health Perspect 104(4):362–369, PMID: 8732939, 10.1289/ehp.96104362. - DOI - PMC - PubMed
1. Andreotti G, Beane Freeman LE, Hou L, Coble J, Rusiecki J, Hoppin JA, et al. . 2009. Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study cohort. Int J Cancer 124(10):2495–2500, PMID: 19142867, 10.1002/ijc.24185. - DOI - PMC - PubMed
1. Bell CG, Lowe R, Adams PD, Baccarelli AA, Beck S, Bell JT, et al. . 2019. DNA methylation aging clocks: challenges and recommendations. Genome Biol 20(1):249, PMID: 31767039, 10.1186/s13059-019-1824-y. - DOI - PMC - PubMed
1. Benitez-Trinidad AB, Medina-Dáaz IM, Bernal-Hernández YY, Barrón-Vivanco BS, González-Arias CA, Herrera-Moreno JF, et al. . 2018. Relationship between LINE-1 methylation pattern and pesticide exposure in urban sprayers. Food Chem Toxicol 113:125–133, PMID: 29374593, 10.1016/j.fct.2018.01.035. - DOI - PubMed
1. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57(1):289–300, 10.1111/j.2517-6161.1995.tb02031.x. - DOI

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

[1] Alavanja MC, Sandler DP, McMaster SB, Zahm SH, McDonnell CJ, Lynch CF, et al. . 1996. The Agricultural Health Study. Environ Health Perspect 104(4):362–369, PMID: 8732939, 10.1289/ehp.96104362. - DOI - PMC - PubMed

[2] Alavanja MC, Sandler DP, McMaster SB, Zahm SH, McDonnell CJ, Lynch CF, et al. . 1996. The Agricultural Health Study. Environ Health Perspect 104(4):362–369, PMID: 8732939, 10.1289/ehp.96104362. - DOI - PMC - PubMed

[3] Andreotti G, Beane Freeman LE, Hou L, Coble J, Rusiecki J, Hoppin JA, et al. . 2009. Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study cohort. Int J Cancer 124(10):2495–2500, PMID: 19142867, 10.1002/ijc.24185. - DOI - PMC - PubMed

[4] Andreotti G, Beane Freeman LE, Hou L, Coble J, Rusiecki J, Hoppin JA, et al. . 2009. Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study cohort. Int J Cancer 124(10):2495–2500, PMID: 19142867, 10.1002/ijc.24185. - DOI - PMC - PubMed

[5] Bell CG, Lowe R, Adams PD, Baccarelli AA, Beck S, Bell JT, et al. . 2019. DNA methylation aging clocks: challenges and recommendations. Genome Biol 20(1):249, PMID: 31767039, 10.1186/s13059-019-1824-y. - DOI - PMC - PubMed

[6] Bell CG, Lowe R, Adams PD, Baccarelli AA, Beck S, Bell JT, et al. . 2019. DNA methylation aging clocks: challenges and recommendations. Genome Biol 20(1):249, PMID: 31767039, 10.1186/s13059-019-1824-y. - DOI - PMC - PubMed

[7] Benitez-Trinidad AB, Medina-Dáaz IM, Bernal-Hernández YY, Barrón-Vivanco BS, González-Arias CA, Herrera-Moreno JF, et al. . 2018. Relationship between LINE-1 methylation pattern and pesticide exposure in urban sprayers. Food Chem Toxicol 113:125–133, PMID: 29374593, 10.1016/j.fct.2018.01.035. - DOI - PubMed

[8] Benitez-Trinidad AB, Medina-Dáaz IM, Bernal-Hernández YY, Barrón-Vivanco BS, González-Arias CA, Herrera-Moreno JF, et al. . 2018. Relationship between LINE-1 methylation pattern and pesticide exposure in urban sprayers. Food Chem Toxicol 113:125–133, PMID: 29374593, 10.1016/j.fct.2018.01.035. - DOI - PubMed

[9] Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57(1):289–300, 10.1111/j.2517-6161.1995.tb02031.x. - DOI

[10] Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57(1):289–300, 10.1111/j.2517-6161.1995.tb02031.x. - DOI

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous