Rathod Aniruddha, Zhang Hongmei, Arshad Syed Hasan, Ewart Susan, Relton Caroline L, Karmaus Wilfried, Holloway John W
Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38111, USA.
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
J Pers Med. 2022 Feb 2;12(2):202. doi: 10.3390/jpm12020202.
The role of epigenetics in the pathogenesis of asthma acquisition in adolescence and post-adolescence has been unknown. We carried out a longitudinal epigenome-wide association study, using data from the Isle of Wight Birth Cohort (IOWBC). To improve statistical power, we first screened CpGs based on associations of DNA methylation (DNAm) at an age of 10 years (pre-adolescence) with asthma acquisition at 10-18 years (during adolescence). A logistic regression with repeated measures was applied to CpGs that passed screening to examine the associations of pre-adolescence DNAm with asthma acquisition from 10-18 years and 18-26 years, with an interaction term to evaluate transition period specificity. Findings were further tested in an independent birth cohort, ALSPAC. In total, 205 CpGs (with 150 being females) showed associations with asthma acquisition (main or interaction effects) at FDR = 0.05 in IOWBC, of which 112 (90 being females) showed consistent associations in the ALSPAC. Genes that the identified CpGs were mapped to, e.g., and , have been shown to be associated with the risk of asthma. Our findings indicated that DNAm at specific CpGs was associated with asthma acquisition. CpGs showing such associations were likely to be different between males and females and, at certain CpGs, were unique to a specific transition period.
表观遗传学在青少年期及青少年后期哮喘发病机制中的作用尚不清楚。我们利用怀特岛出生队列（IOWBC）的数据进行了一项纵向全表观基因组关联研究。为了提高统计效力，我们首先根据10岁（青春期前）时的DNA甲基化（DNAm）与10至18岁（青春期期间）哮喘发病的关联来筛选CpG。对通过筛选的CpG应用重复测量的逻辑回归，以检验青春期前DNAm与10至18岁和18至26岁哮喘发病的关联，并使用一个交互项来评估过渡期特异性。研究结果在独立的出生队列ALSPAC中进一步验证。在IOWBC中，共有205个CpG（其中150个为女性）在FDR = 0.05时显示与哮喘发病有关联（主要或交互作用），其中112个（90个为女性）在ALSPAC中显示出一致的关联。已鉴定出的CpG所映射到的基因，如 和 ，已被证明与哮喘风险相关。我们的研究结果表明，特定CpG处的DNAm与哮喘发病有关联。显示这种关联的CpG在男性和女性之间可能不同，并且在某些CpG处，是特定过渡期所特有的。
