PDF(Pubmed)
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.
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.
摘要：
已经提出了青春期新生儿DNA甲基化（DNAm）与哮喘获得（AA）之间的关联。肺功能（LF）已被证明与哮喘风险及其严重程度有关。然而,LF在DNAm和AA之间的关联中的作用尚不清楚，DNAm和AA之间的关联是否与DNAm和LF之间的关联是未知的。我们通过评估青春期前LF和青春期AA的新生儿表观遗传特征来解决这个问题。以及它们的生物学途径和过程。我们研究的主要医学意义在于推进对哮喘早期生命起源的理解。通过研究新生儿的表观遗传标记及其与青春期前肺功能的关系，我们旨在发现哮喘风险的潜在早期生物标志物.这可以促进早期检测和干预策略。此外,探索将早期肺功能与后期哮喘发展联系起来的生物学途径可以提供对疾病发病机制的见解，可能导致新的治疗目标。
方法：该研究基于怀特岛出生队列（IOWBC）。包括在出生时具有DNAm数据并且在10岁时没有哮喘的女性受试者(n=249)。应用R包ttScreening来鉴定可能与10至18岁的AA和10岁的LF相关的CpG(FEV1，FVC，和FEV1/FVC），分别。检查了AA和LF之间确定的CpG的协议，以及它们通过R功能gometh的生物学途径和过程。我们在一个独立的队列中测试了这些发现，雅芳父母和子女纵向研究(ALSPAC)，检查整体可复制性。
结果：在IOWBC中，检测到292个CpG与AA相关的DNAm和1517个LF的独特CpG（FEV1为514，FVC为436，FEV1/FVC为408),有一个重叠的CpG，AA和LF之间的cg23642632（NCKAP1）。在IOWBC鉴定的CpG中，我们在ALSPAC中进行了进一步测试,在FVC中观察到两个队列在关联方向和统计学显著性方面的一致性最高.表观遗传富集分析表明AA和LF之间的生物学途径和过程中存在非特异性连接。
结论：本研究表明FEV1、FVC、FEV1/FVC（作为LF的客观指标）和AA（哮喘的发病率）在出生时可能有自己特定的表观遗传特征和生物学途径。需要更多的复制来充分理解DNAm之间的复杂性，肺功能,和哮喘收购。
方法：该研究基于怀特岛出生队列（IOWBC）。包括在出生时具有DNAm数据并且在10岁时没有哮喘的女性受试者(n=249)。应用R包ttScreening来鉴定可能与10至18岁的AA和10岁的LF相关的CpG(FEV1，FVC，和FEV1/FVC），分别。检查了AA和LF之间确定的CpG的协议，以及它们通过R功能gometh的生物学途径和过程。我们在一个独立的队列中测试了这些发现，雅芳父母和子女纵向研究(ALSPAC)，检查整体可复制性。
结果：在IOWBC中，检测到292个CpG与AA相关的DNAm和1517个LF的独特CpG（FEV1为514，FVC为436，FEV1/FVC为408),有一个重叠的CpG，AA和LF之间的cg23642632（NCKAP1）。在IOWBC鉴定的CpG中，我们在ALSPAC中进行了进一步测试,在FVC中观察到两个队列在关联方向和统计学显著性方面的一致性最高.表观遗传富集分析表明AA和LF之间的生物学途径和过程中存在非特异性连接。
结论：本研究表明FEV1、FVC、FEV1/FVC（作为LF的客观指标）和AA（哮喘的发病率）在出生时可能有自己特定的表观遗传特征和生物学途径。需要更多的复制来充分理解DNAm之间的复杂性，肺功能,和哮喘收购。
