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Indoor Allergen Exposure, DNA Methylation, and Childhood Asthma

Alamoudi, Banan
http://orcid.org/0000-0003-1351-7271
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1657796719340125

Abstract Details

2022, PhD, University of Cincinnati, Medicine: Epidemiology (Environmental Health).
Background: While the link between allergens and asthma has been studied extensively, less is known about the mechanisms by which indoor allergen (IA) exposure predisposes children to asthma and wheezing phenotypes. The relation between indoor allergens, DNA methylation, asthma, and wheezing phenotypes were examined in a well-established birth cohort: the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). Objectives: To assess the relationship between indoor allergen exposure during early childhood (age 1) and DNA methylation at age 12. To identify DNA methylation profiles associated with asthma and wheezing phenotypes. To evaluate whether DNA methylation mediates the association between IA exposure and asthma, persistent asthma, or wheezing phenotypes. Methods: Indoor allergens (Alternaria, cat, dog, house dust mite, and cockroach allergens) and 36 species of mold of the environmental relative moldiness index (ERMI) were collected from house dust samples and quantified at age 1. Asthma and wheezing were assessed at 12 years; persistent asthma was defined as having asthma symptoms at age 12 and a prior diagnosis of asthma at age 7. DNA methylation was measured from whole blood collected at age 12 and quantified using the Infinium Methylation EPIC (850k) BeadChip microarray. An epigenome-wide association study was performed to detect differentially methylated CpGs (DMCs) and regions (DMRs) associated with IAs exposure and ERMI and then interrogated whether the DMCs were associated with asthma, persistent asthma, and wheezing phenotypes at age 12 years. Robust linear regression models were used to estimate the associations between IA exposure and DNA methylation. Baron and Kenny’s steps were used to detect whether specific DMCs act as mediators influencing the relationship between IA exposure or ERMI with asthma, its persistence, and wheezing phenotypes. Results: From 262 CCAAPS children, 15 DMCs and 3 DMRs were associated with exposure to three or more IAs. From 148 children, 7 DMCs and 1 DMR were associated with a high ERMI. Some of the DMCs were associated with asthma, persistent asthma, and/or wheezing phenotypes. Eight significant DMCs (5 from the 15 DMCs and 3 from the 7 DMCs) were found to be hypomethylated and annotated to the following genes: TMEM201, GALNTL4, LRBA, NPTN, CARD9, DNLZ, and PTPN14. The study found 161 DMCs and 21 DMRs associated with IA exposure annotated to genes involved in metabolism pathways. The direct effects of exposure to = 3 IA and ERMI were investigated with the respiratory outcomes. All were non-significant except for the relation of ERMI exposure with persistent asthma. There was no evidence of mediation by DMCs in the ERMI model predicting persistent asthma. However, the effect of ERMI was decreased after adding cg17465338 as a mediator in the model (path c) compared with the direct effect path (ß = 0.07 vs. ß = 0.09, p = 0.027 vs. p = 0.111, respectively) Conclusions: Exposure to IAs and ERMI during early childhood was associated with differential methylation at several loci; some of these loci were also associated with asthma and wheezing. The findings of this study not only suggest potential mechanisms and pathways by which IA exposure may impact the development of asthma but also underscores the importance of reducing IA exposure through intervention to improve and/or prevent poor respiratory health.
Kelly Brunst, Ph.D. (Committee Member)
Patrick Ryan, Ph.D. (Committee Member)
Tiina Reponen, Ph.D. (Committee Member)
Liang Niu, Ph.D. (Committee Member)
161 p.
Epidemiology
indoor allergens; asthma; DNA methylation; epigenetics; environmental; epidemiology

Recommended Citations

Citations

  • Alamoudi, B. (2022). Indoor Allergen Exposure, DNA Methylation, and Childhood Asthma [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1657796719340125

    APA Style (7th edition)

  • Alamoudi, Banan. Indoor Allergen Exposure, DNA Methylation, and Childhood Asthma. 2022. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1657796719340125.

    MLA Style (8th edition)

  • Alamoudi, Banan. "Indoor Allergen Exposure, DNA Methylation, and Childhood Asthma." Doctoral dissertation, University of Cincinnati, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1657796719340125

    Chicago Manual of Style (17th edition)

ucin1657796719340125
41
© 2022, some rights reserved.Creative Commons License Indoor Allergen Exposure, DNA Methylation, and Childhood Asthma by Banan Alamoudi is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.