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

Dakotah Feil; Sarina Abrishamcar; Grace M Christensen; Aneesa Vanker; Nastassja Koen; Anna Kilanowski; Nadia Hoffman; Catherine J Wedderburn; Kirsten A Donald; Michael S Kobor; Heather J Zar; Dan J Stein; Anke Hüls

doi:10.1186/s13148-023-01444-6

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

Clin Epigenetics. 2023 Feb 28;15(1):31. doi: 10.1186/s13148-023-01444-6.

Authors

Dakotah Feil¹, Sarina Abrishamcar¹, Grace M Christensen¹, Aneesa Vanker², Nastassja Koen^{3

4

5}, Anna Kilanowski^{1

6

7

8}, Nadia Hoffman^{3

4}, Catherine J Wedderburn^{2

3

9}, Kirsten A Donald^{2

3}, Michael S Kobor^{10

11

12}, Heather J Zar², Dan J Stein^{3

4

5}, Anke Hüls^{13

14}

Affiliations

¹ Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA, 30322, USA.
² Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, SA and SA-MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
³ Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁴ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
⁵ South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
⁶ German Research Center for Environmental Health, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
⁷ Institute for Medical Information Processing, Biometry, and Epidemiology, Pettenkofer School of Public Health, LMU Munich, Munich, Germany.
⁸ Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany.
⁹ Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.
¹⁰ Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
¹¹ BC Children's Hospital Research Institute, Vancouver, BC, Canada.
¹² Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada.
¹³ Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA, 30322, USA. anke.huels@emory.edu.
¹⁴ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. anke.huels@emory.edu.

Abstract

Background: Exposure to indoor air pollution during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may explain this link. In this study, we employed three high-dimensional mediation analysis methods (HIMA, DACT, and gHMA) followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between indoor air pollution and neurodevelopmental delay. Analyses were performed using data from 142 mother to child pairs from a South African birth cohort, the Drakenstein Child Health Study. DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at age 2 years using the Bayley Scores of Infant and Toddler Development, 3rd edition across four domains (cognitive development, general adaptive behavior, language, and motor function). Particulate matter with an aerodynamic diameter of 10 μm or less (PM₁₀) was measured inside participants' homes during the second trimester of pregnancy.

Results: A total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators of the association between PM₁₀ and cognitive neurodevelopment. The estimated proportion mediated (95%-confidence interval) ranged from 0.29 [0.01, 0.86] for cg00694520 to 0.54 [0.11, 1.56] for cg05023582.

Conclusions: Our findings suggest that DNAm may mediate the association between prenatal PM₁₀ exposure and cognitive neurodevelopment. DYRK1A and several genes that our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1, are associated with biological pathways implicated in cognitive neurodevelopment and three of our identified CpG sites (cg23560546 [DAPL1], cg22572779 [C6orf218], cg15000966 [NT5C]) have been previously associated with fetal brain development. These findings are novel and add to the limited literature investigating the relationship between indoor air pollution, DNAm, and neurodevelopment, particularly in low- and middle-income country settings and non-white populations.

Keywords: Cord blood; Epigenetics; Neurodevelopment; Newborn DNA methylation; Particulate matter.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Air Pollution, Indoor* / adverse effects
Birth Cohort
Child, Preschool
DNA Methylation*
Developmental Disabilities* / epidemiology
Female
Humans
Infant
Pregnancy
South Africa / epidemiology

Abstract

Publication types

MeSH terms

Grants and funding