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Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
Newborn DNA methylation and asthma acquisition across adolescence and early adulthood
Liang Li1, John W Holloway2, Susan Ewart3
1Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, Tennessee, USA.
Insights
Newborn DNA methylation (DNAm) patterns can predict asthma development later in life. Researchers identified eight specific DNAm sites associated with asthma acquisition in females during adolescence and young adulthood.
Area of Science:
- Epigenetics and Developmental Origins of Health and Disease (DOHaD).
Background:
- The relationship between newborn DNA methylation (DNAm) and the later development of asthma is not well understood.
- Asthma acquisition across adolescence and early adult life remains a significant public health concern.
Purpose of the Study:
- To identify specific epigenetic biomarkers in newborns that can predict asthma development during adolescence or young adulthood.
- To investigate genome-wide DNA methylation patterns associated with asthma acquisition.
Main Methods:
- Utilized the Isle of Wight Birth Cohort (IOWBC) and the Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts.
- Employed genome-scale screening of cytosine-phosphate-guanine (CpG) sites for differential methylation and association with asthma.
- Applied logistic regression models to identify and validate candidate epigenetic biomarkers.
Main Results:
- Identified one biological pathway linked to asthma acquisition in adolescent females.
- Discovered eight specific CpG sites associated with asthma acquisition in females during adolescence and young adulthood, replicated in an independent cohort.
- Found temporal consistency in DNA methylation at identified CpGs and associations with gene expression in females.
Conclusions:
- Eight CpG sites on specific genes (LHX5, IL22RA2, SOX11, CBX4, ACPT, CFAP46, MUC4, and ATP1B2) show potential as epigenetic biomarkers for predicting asthma in females.
- These findings offer novel insights into the early epigenetic signatures of asthma development.
Background:
Little is known about the association of newborn DNA methylation (DNAm) with asthma acquisition across adolescence and early adult life.
Objective:
We aim to identify epigenetic biomarkers in newborns for asthma acquisition during adolescence or young adulthood.
Methods:
The Isle of Wight Birth Cohort (IOWBC) (n = 1456) data at ages 10, 18 and 26 years were assessed. To screen cytosine-phosphate-guanine site (CpGs) potentially associated with asthma acquisition, at the genome scale, we examined differentially methylated regions (DMR) using dmrff R package and individual CpG sites using linear regression on such associations. For CpGs that passed screening, we examined their enrichment in biological pathways using their mapping genes and tested their associations with asthma acquisitions using logistic regressions. Findings in IOWBC were tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.
Results:
In total, 2636 unique CpGs passed screening, based on which we identified one biological pathway linked to asthma acquisition during adolescence in females (FDR adjusted p-value = .003 in IOWBC). Via logistic regressions, for females, four CpGs were shown to be associated with asthma acquisition during adolescence, and another four CpGs with asthma acquisition in young adulthood (FDR adjusted p-value < .05 in IOWBC) and these eight CpGs were replicated in ALSPAC (all p-values < .05). DNAm at all the identified CpGs was shown to be temporally consistent, and at six of the CpGs was associated with expressions of adjacent or mapping genes in females (all p-values < .05). For males, 622 CpGs were identified in IOWBC (FDR = 0.01), but these were not tested in ALSPAC due to small sample sizes.
Conclusion And Clinical Relevance:
Eight CpGs on LHX5, IL22RA2, SOX11, CBX4, ACPT, CFAP46, MUC4, and ATP1B2 genes have the potential to serve as candidate epigenetic biomarkers in newborns for asthma acquisition in females during adolescence or young adulthood.
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