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Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure

Individuals within genetically diverse populations display broad susceptibility differences upon chemical exposures. Understanding the role of gene-environment interactions (GxE) in differential susceptibility to an expanding exposome is key to protecting public health. However, a chemical’s potenti...

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Autores principales: Thunga, Preethi, Truong, Lisa, Rericha, Yvonne, Du, Jane La, Morshead, Mackenzie, Tanguay, Robyn L., Reif, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781692/
https://www.ncbi.nlm.nih.gov/pubmed/36548602
http://dx.doi.org/10.3390/toxics10120769
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author Thunga, Preethi
Truong, Lisa
Rericha, Yvonne
Du, Jane La
Morshead, Mackenzie
Tanguay, Robyn L.
Reif, David M.
author_facet Thunga, Preethi
Truong, Lisa
Rericha, Yvonne
Du, Jane La
Morshead, Mackenzie
Tanguay, Robyn L.
Reif, David M.
author_sort Thunga, Preethi
collection PubMed
description Individuals within genetically diverse populations display broad susceptibility differences upon chemical exposures. Understanding the role of gene-environment interactions (GxE) in differential susceptibility to an expanding exposome is key to protecting public health. However, a chemical’s potential to elicit GxE is often not considered during risk assessment. Previously, we’ve leveraged high-throughput zebrafish (Danio rerio) morphology screening data to reveal patterns of potential GxE effects. Here, using a population genetics framework, we apportioned variation in larval behavior and gene expression in three different PFHxA environments via mixed-effect modeling to assess significance of GxE term. We estimated the intraclass correlation (ICC) between full siblings from different families using one-way random-effects model. We found a significant GxE effect upon PFHxA exposure in larval behavior, and the ICC of behavioral responses in the PFHxA exposed population at the lower concentration was 43.7%, while that of the control population was 14.6%. Considering global gene expression data, a total of 3746 genes showed statistically significant GxE. By showing evidence that heritable genetics are directly affecting gene expression and behavioral susceptibility of individuals to PFHxA exposure, we demonstrate how standing genetic variation in a heterogeneous population such as ours can be leveraged to test for potential GxE.
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spelling pubmed-97816922022-12-24 Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure Thunga, Preethi Truong, Lisa Rericha, Yvonne Du, Jane La Morshead, Mackenzie Tanguay, Robyn L. Reif, David M. Toxics Article Individuals within genetically diverse populations display broad susceptibility differences upon chemical exposures. Understanding the role of gene-environment interactions (GxE) in differential susceptibility to an expanding exposome is key to protecting public health. However, a chemical’s potential to elicit GxE is often not considered during risk assessment. Previously, we’ve leveraged high-throughput zebrafish (Danio rerio) morphology screening data to reveal patterns of potential GxE effects. Here, using a population genetics framework, we apportioned variation in larval behavior and gene expression in three different PFHxA environments via mixed-effect modeling to assess significance of GxE term. We estimated the intraclass correlation (ICC) between full siblings from different families using one-way random-effects model. We found a significant GxE effect upon PFHxA exposure in larval behavior, and the ICC of behavioral responses in the PFHxA exposed population at the lower concentration was 43.7%, while that of the control population was 14.6%. Considering global gene expression data, a total of 3746 genes showed statistically significant GxE. By showing evidence that heritable genetics are directly affecting gene expression and behavioral susceptibility of individuals to PFHxA exposure, we demonstrate how standing genetic variation in a heterogeneous population such as ours can be leveraged to test for potential GxE. MDPI 2022-12-09 /pmc/articles/PMC9781692/ /pubmed/36548602 http://dx.doi.org/10.3390/toxics10120769 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Thunga, Preethi
Truong, Lisa
Rericha, Yvonne
Du, Jane La
Morshead, Mackenzie
Tanguay, Robyn L.
Reif, David M.
Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure
title Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure
title_full Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure
title_fullStr Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure
title_full_unstemmed Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure
title_short Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure
title_sort utilizing a population-genetic framework to test for gene-environment interactions between zebrafish behavior and chemical exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781692/
https://www.ncbi.nlm.nih.gov/pubmed/36548602
http://dx.doi.org/10.3390/toxics10120769
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