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Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.

ABSTRACT: We examined risks associated with joint exposure of gene variants and pesticides.Analyses included 189 cases and 390 male controls born from 1991 to 2003 in California's San Joaquin Valley. We used logistic regression to examine risks associated with joint exposures of gene variants and pesticides that our previous work identified as associated with hypospadias. Genetic variables were based on variants in DGKK, genes involved in sex steroid synthesis/metabolism, and genes involved in genital tubercle development. Pesticide exposure was based on residential proximity to commercial agricultural pesticide applications.Odds ratios (ORs) were highest among babies with joint exposures, who had two- to fourfold increased risks; for example, the OR was 3.7 (95% confidence interval [CI], 0.8-16.5) among subjects with the risk-associated DGKK haplotype and pesticide exposure; OR, 1.5 (95% CI, 0.7-3.1) among subjects with the haplotype and no pesticide exposure; and OR, 0.9 (95% CI, 0.5-1.6) among subjects without the haplotype but with pesticide exposure, relative to subjects with neither. However, results did not provide statistical evidence that these risks were significantly greater than expected on an additive scale, relative to risks associated with one exposure at a time.We observed elevated risks associated with joint exposures to selected pesticides and genetic variants but no statistical evidence for interaction. Birth Defects Research (Part A) 106:653-658, 2016. © 2016 Wiley Periodicals, Inc.

SUBMITTER: Carmichael SL

PROVIDER: S-EPMC4983249 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.

Carmichael Suzan L SL Yang Wei W Ma Chen C Roberts Eric E Kegley Susan S English Paul P Lammer Edward J EJ Witte John S JS Shaw Gary M GM

Birth defects research. Part A, Clinical and molecular teratology 20160421 8

<h4>Background</h4>We examined risks associated with joint exposure of gene variants and pesticides.<h4>Methods</h4>Analyses included 189 cases and 390 male controls born from 1991 to 2003 in California's San Joaquin Valley. We used logistic regression to examine risks associated with joint exposures of gene variants and pesticides that our previous work identified as associated with hypospadias. Genetic variables were based on variants in DGKK, genes involved in sex steroid synthesis/metabolism ...[more]

PMID: 27098078

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Project description:BackgroundPrenatal pesticide exposure has been associated with poorer neurodevelopment during childhood, which could lead to greater risk-taking behaviors and delinquency in adolescence. This association may be augmented by adversity exposure.ObjectivesEvaluate the relationship between prenatal pesticide exposure and risk-taking behavior in young adults at 18-years of age. Assess whether adversity exposure modifies these associations.MethodsParticipants included mother-child dyads (n = 467) enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study, a longitudinal birth cohort set in the agricultural Salinas Valley of California. We estimated agricultural pesticide use within one km of maternal residences during pregnancy using a geographic information system, residential addresses, and California's Pesticide Use Reporting data. We used Bayesian hierarchical regression to evaluate associations of prenatal exposure to a mixture of 11 neurotoxic pesticides with self-reported police encounters, risk-taking behaviors, and unique types and frequency of delinquent acts. We also evaluated effect modification of these relationships by adversity exposure.ResultsWe observed generally null associations of neurotoxic pesticide use with risk-taking behaviors. Prenatal residential proximity to chlorpyrifos use was associated with higher risk of a police encounter, a delinquent act, and higher incidence of both unique types of acts committed and total frequency of delinquent acts. Prenatal residential proximity to dimethoate use was associated with a higher incidence of police encounters and methomyl with a higher risk of committing a delinquent act. There were no consistent differences when stratified by the number of adverse childhood experiences.ConclusionsWe observed mostly null associations between prenatal residential proximity to agricultural pesticide use and risk-taking behaviors at age 18, with little evidence of effect modification by childhood adversity. There were suggestive associations for chlorpyrifos use with having any police encounter and with all measures of delinquent acts that warrant confirmation in other studies.

Project description:BackgroundResidential proximity to agricultural pesticide use has been associated with neural tube defects and autism, but more subtle outcomes such as cognition have not been studied.ObjectivesWe evaluated the relationship between prenatal residential proximity to agricultural use of potentially neurotoxic pesticides and neurodevelopment in 7-year-old children.MethodsParticipants included mothers and children (n=283) living in the agricultural Salinas Valley of California enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. We estimated agricultural pesticide use within 1 km of maternal residences during pregnancy using a geographic information system, residential location, and California’s comprehensive agricultural Pesticide Use Report data. We used regression models to evaluate prenatal residential proximity to agricultural use of five potentially neurotoxic pesticide groups (organophosphates, carbamates, pyrethroids, neonicotinoids, and manganese fungicides) and five individual organophosphates (acephate, chlorpyrifos, diazinon, malathion, and oxydemeton-methyl) and cognition in 7-year-old children. All models included prenatal urinary dialkyl phosphate metabolite concentrations.ResultsWe observed a decrease of 2.2 points [95% confidence interval (CI): −3.9, −0.5] in Full-Scale IQ and 2.9 points (95% CI: −4.4, −1.3) in Verbal Comprehension for each standard deviation increase in toxicity-weighted use of organophosphate pesticides. In separate models, we observed similar decrements in Full-Scale IQ with each standard deviation increase of use for two organophosphates (acephate and oxydemeton-methyl) and three neurotoxic pesticide groups (pyrethroids, neonicotinoids, and manganese fungicides).ConclusionsThis study identified potential relationships between maternal residential proximity to agricultural use of neurotoxic pesticides and poorer neurodevelopment in children. https://doi.org/10.1289/EHP504.

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Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.

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Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.

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