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Epigenetic Features in Newborns Associated with Preadolescence Lung Function and Asthma Acquisition during
Mohammad Nahian Ferdous Abrar1, Yu Jiang1, Hongmei Zhang1
1Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38152, USA.
Insights
Newborn DNA methylation (DNAm) shows distinct epigenetic features related to lung function (LF) and asthma acquisition (AA) in adolescence. These associations appear to involve separate biological pathways, suggesting unique early life origins for each outcome.
Area of Science:
- Epigenetics and Environmental Health
- Respiratory Medicine
- Pediatric Asthma Research
Background:
- Newborn DNA methylation (DNAm) is linked to adolescent asthma acquisition (AA).
- Lung function (LF) is associated with asthma risk and severity.
- The interplay between DNAm, LF, and AA remains unclear.
Purpose of the Study:
- To investigate newborn epigenetic markers associated with preadolescent LF and adolescent AA.
- To identify overlapping and distinct biological pathways for LF and AA.
- To advance understanding of early life origins of asthma and identify potential biomarkers.
Main Methods:
- Analysis of the Isle of Wight Birth Cohort (IOWBC) and Avon Longitudinal Study of Parents and Children (ALSPAC).
- Identification of CpGs associated with AA and LF (FEV1, FVC, FEV1/FVC) using ttScreening.
- Examination of CpG agreement and biological pathway enrichment using gometh.
Main Results:
- 292 CpGs linked to AA and 1517 CpGs to LF were identified in IOWBC.
- Only one overlapping CpG (cg23642632) was found between AA and LF.
- Epigenetic enrichment analyses revealed non-specific biological pathway connections between AA and LF.
Conclusions:
- FEV1, FVC, FEV1/FVC, and AA appear to have distinct epigenetic signatures at birth.
- Specific biological pathways may underlie LF and AA independently.
- Further replication studies are needed to fully elucidate the complex relationships between DNAm, LF, and AA.
Abstract:
The association between newborn DNA methylation (DNAm) and asthma acquisition (AA) during adolescence has been suggested. Lung function (LF) has been shown to be associated with asthma risk and its severity. However, the role of LF in the associations between DNAm and AA is unclear, and it is also unknown whether the association between DNAm and AA is consistent with that between DNAm and LF. We address this question through assessing newborn epigenetic features of preadolescence LF and of AA during adolescence, along with their biological pathways and processes. Our study's primary medical significance lies in advancing the understanding of asthma's early life origins. By investigating epigenetic markers in newborns and their association with lung function in preadolescence, we aim to uncover potential early biomarkers of asthma risk. This could facilitate earlier detection and intervention strategies. Additionally, exploring biological pathways linking early lung function to later asthma development can offer insights into the disease's pathogenesis, potentially leading to novel therapeutic targets.
Methods:
The study was based on the Isle of Wight Birth cohort (IOWBC). Female subjects with DNAm data at birth and with no asthma at age 10 years were included (n = 249). The R package ttScreening was applied to identify CpGs potentially associated with AA from 10 to 18 years and with LF at age 10 (FEV1, FVC, and FEV1/FVC), respectively. Agreement in identified CpGs between AA and LF was examined, along with their biological pathways and processes via the R function gometh. We tested the findings in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine overall replicability.
Results:
In IOWBC, 292 CpGs were detected with DNAm associated with AA and 1517 unique CpGs for LF (514 for FEV1, 436 for FVC, 408 for FEV1/FVC), with one overlapping CpG, cg23642632 (NCKAP1) between AA and LF. Among the IOWBC-identified CpGs, we further tested in ALSPAC and observed the highest agreement between the two cohorts in FVC with respect to the direction of association and statistical significance. Epigenetic enrichment analyses indicated non-specific connections in the biological pathways and processes between AA and LF.
Conclusions:
The present study suggests that FEV1, FVC, and FEV1/FVC (as objective measures of LF) and AA (incidence of asthma) are likely to have their own specific epigenetic features and biological pathways at birth. More replications are desirable to fully understand the complexity between DNAm, lung function, and asthma acquisition.
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