DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort Pubblico

Abstract

Exposure to indoor air pollution (IAP) during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may help explain this link. In this study, we employ three high-dimensional mediation analysis (HIMA, DACt, and gHMA) methods followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between IAP and neurodevelopmental delay. Analyses were performed using data from 142 mother-child pairs from the South African Drakenstein Child Health Study (DCHS). DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at 2 years of age with the Bayley Scores of Infant and Toddler Development (BSID-III). Particulate matter with an aerodynamic diameter of 10mm or less (PM10) was collected from devices placed in participants’ homes during the second trimester of pregnancy. A total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators. Proportion mediated estimates (95%-confidence interval) ranged from 0.29 (0.014,0.86) for cg00694520 to 0.54 (0.11,1.56) for cg05023582. DYRK1A and several genes our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1 are associated with biological pathways implicated in neurodevelopment. These findings suggest that DNAm might mediate the association between prenatal indoor PM10 exposure and cognitive neurodevelopment.

Table of Contents

Section | Page

Introduction | 8

Materials & Methods | 11

Results | 18

Discussion | 20

Conclusion | 29

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health
Parola chiave	newborn DNA methylation epigenetics particulate matter Bayley Scales of Infant and Toddler Development (BSID-III) cord blood
Committee Chair / Thesis Advisor	Huls, Anke, Emory University

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