A Pathway-Based Genetic Score for Oxidative Stress: An Indicator of Host Vulnerability to Phthalate-Associated Adverse Neurodevelopment
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Le résumé fourni par la source
The developing brain is highly sensitive to environmental disturbances, and adverse exposures can act through oxidative stress. Given that oxidative stress susceptibility is determined partly by genetics, multiple studies have employed genetic scores to explore the role of oxidative stress in human disease. However, traditional approaches to genetic score construction face a range of challenges, including a lack of interpretability, bias towards the disease outcome, and often overfitting to the study they were derived on. Here, we develop an alternative strategy by first generating a genetic pathway function score for oxidative stress (gPFSox) based on the transcriptional activity levels of the oxidative stress response pathway in brain and other tissue types. Then, in the Barwon Infant Study (BIS), a population-based birth cohort (n = 1074), we show that a high gPFSox, indicating reduced ability to counter oxidative stress, is linked to higher autism spectrum disorder risk and higher parent-reported autistic traits at age 4 years, with AOR values (per 2 additional pro-oxidant alleles) of 2.10 (95% CI (1.12, 4.11); p = 0.024) and 1.42 (95% CI (1.02, 2.01); p = 0.041), respectively. Past work in BIS has reported higher prenatal phthalate exposure at 36 weeks of gestation associated with offspring autism spectrum disorder. In this study, we examine combined effects and show a consistent pattern of increased neurodevelopmental problems for individuals with both a high gPFSox and high prenatal phthalate exposure across a range of outcomes, including high gPFSox and high DEHP levels against autism spectrum disorder (attributable proportion due to interaction 0.89; 95% CI (0.62, 1.16); p < 0.0001). The results highlight the utility of this novel functional genetic score and add to the growing evidence implicating gestational phthalate exposure in adverse neurodevelopment.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A Pathway-Based Genetic Score for Oxidative Stress: An Indicator of Host Vulnerability to Phthalate-Associated Adverse Neurodevelopment
- Date Crossref
- 29/03/2022
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Florey Institute of Neuroscience and Mental Health pays non établi dans la noticeStructure de recherche
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Royal Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Deakin University pays non établi dans la noticeUniversité ou école supérieure
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The University of Melbourne Murdoch Children’s Research Institute pays non établi dans la noticeUniversité ou école supérieure
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Murdoch Children's Research Institute pays non établi dans la noticeOrganisation à but non lucratif
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Walk Free Foundation pays non établi dans la noticeOrganisation à but non lucratif
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Minderoo Foundation pays non établi dans la noticeOrganisation à but non lucratif
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Children's Medical Research Institute pays non établi dans la noticeStructure de recherche
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The University of Queensland Children’s Health Research Centre pays non établi dans la noticeUniversité ou école supérieure
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Barwon Health pays non établi dans la noticeÉtablissement de santé
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Vrije Universiteit Amsterdam Department of Environment and Health pays non établi dans la noticeUniversité ou école supérieure
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University of Oxford Nuffield Department of Women’s & Reproductive Health pays non établi dans la noticeUniversité ou école supérieure
Florey Institute of Neuroscience and Mental Health, Royal Children's Hospital et Deakin University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.