Evidence map›Paper›PMID 30248838›Full record

ArticleThe Science of the total environment2018

Organophosphate pesticide exposure and differential genome-wide DNA methylation.

Kimberly C Paul, Yu-Hsuan Chuang, Myles Cockburn, Jeff M Bronstein, Steve Horvath, Beate Ritz

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Science of the total environment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 81 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Kimberly C PaulDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA. Electronic address: kimberlyc.paul@gmail.com.
Yu-Hsuan ChuangDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.
Myles CockburnDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, USA.
Jeff M BronsteinDepartment of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA.
Steve HorvathDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA.
Beate RitzDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA. Electronic address: britz@ucla.edu.
University of California, Los Angeles · USUCLA Health · USUniversity of Southern California · US

Funding

Center for Gene-Environment Studies in Parkinson DiseaseU54ES012078 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHESSELET, MARIE-FRANCOISE S · 2002 to 2006
$7.1M
PARKINSON'S DISEASES SUSCEPTIBILITY GENES AND PESTICIDESR01ES010544 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2000 to 2015
$5.7M
Environmental exposure, DNA methylation, and Parkinson's diseaseR21ES024356 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HORVATH, STEVE, RITZ, BEATE R. · 2014 to 2015
$424k
Environmental Predictors of the Overlap of Neurodegenerative Disorders and Metabolic DysfunctionF32ES028087 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAUL, KIMBERLY · 2017 to 2018
$121k
NIEHS NIH HHS F32 ES028087NIEHS NIH HHS R01 ES010544NIEHS NIH HHS R21 ES024356NIEHS NIH HHS U54 ES012078
6 · The paper itself

Abstract

backgroundOrganophosphates (OP) are widely used insecticides that acutely inhibit acetylcholinesterase enzyme activity. There is great interest in improving the understanding of molecular mechanisms related to chronic OP exposure induced toxicity. We aim to elucidate epigenetic changes associated with OP exposure, using untargeted analysis of genome-wide DNA methylation data.

methodsIn a population-based case control study of Parkinson's disease (PD), we assessed ambient OP exposure via residential and workplace proximity to commercial applications. We investigated associations between OP exposure and genome-wide DNA methylation (Illumina 450 k) in 580 blood samples (342 PD patients, 238 controls) and 259 saliva samples (128 patients, 131 controls). To identify differential methylation related to OP exposure, we controlled for age, sex, European ancestry, and PD status; in addition, we stratified by disease status.

resultsWe identified 70 genome-wide significant CpGs, including cg01600516 in ALOX12 (cor = 0.27, p = 1.73E-11) and two CpGs in HLA genes, cg01655658 (cor = -0.24, p = 2.80E-09) in HLA-L (pseudogene) and cg15680603 (cor = 0.20, p = 7.94E-07) in HLA-DPA1. Among the 70 CpGs located in 41 genes, 14 were also differentially methylated in saliva samples. The most overrepresented pathway was the nicotinic acetylcholine receptor signaling pathway (fold enrichment = 15.63, p = 1.01E-03, FDR = 1.64E-01). Expanding to a larger number of genes (CpG p < 5E-04, FDR < 2.25E-01; 1077 CpGs, 662 genes), the most enriched pathway shifted to the muscarinic acetylcholine receptor 1 and 3 signaling pathway (p-value = 5.36E-04, FDR = 4.73E-02). When we stratified by PD status, results were similar. Of the 70 significant CpGs, 63 were detected among both patients and controls and 7 were only associated with OP exposure among patients.

conclusionsThis study finds chronic low-level OP exposure is associated with differential DNA methylation in blood and saliva, both in elderly population controls and PD patients. Our study results suggest that long-term sub-acute OP exposure influences methylation in genes enriched for muscarinic and nicotinic acetylcholine receptor pathways.

Indexed as

DNA MethylationEnvironmental ExposureAgedCase-Control StudiesEpigenesis, GeneticHumansOrganophosphatesPesticidesOrganophosphatesPesticidesAcetylcholine receptor pathwaysDNA methylationEWASOrganophosphates

Identifiers

PMID30248838
PMCPMC6400463
OpenAlexW2883220213

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.