Li Liang, Zhang Hongmei, Holloway John W, Ewart Susan, Relton Caroline L, Arshad S Hasan, Karmaus Wilfried
Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN, USA.
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
ERJ Open Res. 2022 Feb 28;8(1). doi: 10.1183/23120541.00476-2021. eCollection 2022 Jan.
Age of pubertal onset is associated with lung function in adulthood. However, the underlying role of epigenetics as a mediator of this association remains unknown.
DNA methylation (DNAm) in peripheral blood was measured at age 18 years in the Isle of Wight birth cohort (IOWBC) along with data on age of pubertal events, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV) at 26 years. Structural equation models were applied to examine mediation effects of DNAm on the association of age at pubertal events with FVC and FEV. Findings were further tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.
In the IOWBC, for females, 21 cytosine-phosphate-guanine sites (CpGs) were shown to mediate the association of age at puberty with FVC or FEV at 26 years (p<0.05). In males, DNAm at 20 CpGs was found to mediate the association of age at puberty with FVC (p<0.05). At almost all these CpGs, indirect effects (effects of age at pubertal events on FVC or FEV DNAm) contributed a smaller portion to the total effects compared to direct effects ( at cg08680129, ∼22% of the estimated total effect of age at menarche on FVC at age 26 was contributed by an indirect effect). Among the IOWBC-discovered CpGs available in ALSPAC, none of them was replicated in ALSPAC (p>0.05).
Our findings suggest that post-adolescence DNAm in peripheral blood is likely not to mediate the association of age at pubertal onset with young adulthood FVC or FEV.
青春期开始的年龄与成年后的肺功能相关。然而，表观遗传学作为这种关联的介导因素的潜在作用仍不清楚。
在怀特岛出生队列（IOWBC）中，于18岁时测量外周血中的DNA甲基化（DNAm），同时收集26岁时青春期事件的年龄、用力肺活量（FVC）和1秒用力呼气量（FEV）的数据。应用结构方程模型来检验DNAm对青春期事件年龄与FVC和FEV之间关联的介导作用。研究结果在阿冯父母与儿童纵向研究（ALSPAC）队列中进一步验证。
在IOWBC中，对于女性，21个胞嘧啶 - 磷酸 - 鸟嘌呤位点（CpG）被证明介导了青春期年龄与26岁时FVC或FEV之间的关联（p<0.05）。对于男性，发现20个CpG的DNAm介导了青春期年龄与FVC之间的关联（p<0.05）。在几乎所有这些CpG中，与直接效应相比，间接效应（青春期事件年龄对FVC或FEV的影响 通过DNAm介导）在总效应中所占比例较小（在cg08680129位点，初潮年龄对26岁时FVC估计总效应的约22%由间接效应贡献）。在ALSPAC中可获得的IOWBC发现的CpG中，没有一个在ALSPAC中得到重复验证（p>0.05）。
我们的研究结果表明，青春期后外周血中的DNAm可能不会介导青春期开始年龄与青年期FVC或FEV之间的关联。
