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.
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。