DNA Methylation and Asthma Acquisition during Adolescence and Post-Adolescence, an Epigenome-Wide Longitudinal Study

Rathod, Aniruddha; Zhang, Hongmei; Arshad, Syed Hasan; Ewart, Susan; Relton, Caroline L; Karmaus, Wilfried; Holloway, John W.

doi:10.3390/jpm12020202

Cited by 7 publications

(6 citation statements)

References 57 publications

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“…However, a potential increase in our understanding of asthma may lie in investigating the disease to some longitudinal capacity. Two previous studies in the Isle of Wight Birth Cohort (IOWBC) were conducted in 2022, which investigated the association of DNA methylation with asthma acquisition across adolescence and adulthood [44,45]. In each of these studies, several CpGs, with some residing in immune regulatory genes, were identified to be associated with asthma acquisition [44,45].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Signatures of Asthma: A Comprehensive Study of DNA Methylation and Clinical Markers

Van Asselt,

Beck,

Johnson

et al. 2024

Preprint

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Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood samples from 319 participants. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 of these individuals. Principal component analysis (PCA) on the clinical markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates. Results: 221 unique CpGs reached genome-wide significance at timepoint 1 (T1) after Bonferroni correction. PC7 accounted for the majority of associations (204), which correlated with loadings of eosinophil counts and immunoglobulin levels. Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint (T2) identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points (271 in total) yielded a correlation of 0.81. Conclusion: We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to using this robust DNA methylation profile as a new, stable biomarker for asthma.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Signatures of Asthma: A Comprehensive Study of DNA Methylation and Clinical Markers

Van Asselt,

Beck,

Johnson

et al. 2024

Preprint

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“…Hongmei Zhang 2 Hasan Arshad 3,4,5 Susan Ewart 6 Meredith Ray 2 Caroline L. Relton 7,8,9 Wilfried Karmaus 2 John W. Holloway…”

Section: Data Ava I L a B I L I T Y S Tat E M E N Tmentioning

confidence: 99%

“…3 DNA methylation (DNAm) or longitudinal change in DNAm at specific cytosine-phosphate-guanine (CpG) sites is associated with the risk of both atopy and asthma 4,5 or asthma acquisition. 6 The role of atopy in the association of DNAm in newborns with asthma acquisition at a later age is unknown. Utilizing data in the Isle of Wight Birth Cohort (IOWBC), we examined whether pre-adolescence atopy mediates the association of newborn DNAm with asthma acquisition from pre-to post-adolescence.…”

Section: The Association Of Dna Methylation At Birth With Adolescent ...mentioning

confidence: 99%

The association of DNA methylation at birth with adolescent asthma is mediated by atopy

Rathod,

Melaram,

Zhang

et al. 2023

Clin Experimental Allergy

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“…DNAm has been shown to be associated with childhood asthma [ 6 , 7 ]. Furthermore, our previous findings suggested a potential association between DNAm at birth and the acquisition of asthma during adolescence [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…By examining individual CpG sites and differentially methylated regions at birth, eight CpG sites were identified as potential epigenetic biomarkers for asthma acquisition during adolescence [ 15 ]. Another study that investigated the association between DNA methylation at birth and asthma acquisition showed that the associated CpGs were more likely to be different between genders and may also be unique to specific transition periods [ 8 ]. Additionally, a separate study highlighted the role of atopy as a mediator in the relationship between DNA methylation and asthma development during both pre- and post-adolescence [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Features in Newborns Associated with Preadolescence Lung Function and Asthma Acquisition during Adolescence

Abrar,

Jiang,

Zhang

et al. 2024

Epigenomes

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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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DNA Methylation and Asthma Acquisition during Adolescence and Post-Adolescence, an Epigenome-Wide Longitudinal Study

Cited by 7 publications

References 57 publications

Epigenetic Signatures of Asthma: A Comprehensive Study of DNA Methylation and Clinical Markers

Epigenetic Signatures of Asthma: A Comprehensive Study of DNA Methylation and Clinical Markers

The association of DNA methylation at birth with adolescent asthma is mediated by atopy

Epigenetic Features in Newborns Associated with Preadolescence Lung Function and Asthma Acquisition during Adolescence

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