Murphy Therese M, Wong Chloe C Y, Arseneault Louise, Burrage Joe, Macdonald Ruby, Hannon Eilis, Fisher Helen L, Ambler Antony, Moffitt Terrie E, Caspi Avshalom, Mill Jonathan
University of Exeter Medical School, University of Exeter, Exeter, UK.
MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Clin Epigenetics. 2015 Dec 18;7:130. doi: 10.1186/s13148-015-0163-4. eCollection 2015.
Asthma is the most common chronic inflammatory disorder in children. The aetiology of asthma pathology is complex and highly heterogeneous, involving the interplay between genetic and environmental risk factors that is hypothesized to involve epigenetic processes. Our aim was to explore whether methylomic variation in early childhood is associated with discordance for asthma symptoms within monozygotic (MZ) twin pairs recruited from the Environmental Risk (E-Risk) longitudinal twin study. We also aimed to identify differences in DNA methylation that are associated with asthma that develops in childhood and persists into early adulthood as these may represent useful prognostic biomarkers.
We examined genome-wide patterns of DNA methylation in buccal cell samples collected from 37 MZ twin pairs discordant for asthma at age 10. DNA methylation at individual CpG sites demonstrated significant variability within discordant MZ twin pairs with the top-ranked nominally significant differentially methylated position (DMP) located in the HGSNAT gene. We stratified our analysis by assessing DNA methylation differences in a sub-group of MZ twin pairs who remained persistently discordant for asthma at age 18. The top-ranked nominally significant DMP associated with persisting asthma is located in the vicinity of the HLX gene, which has been previously implicated in childhood asthma.
We identified DNA methylation differences associated with childhood asthma in peripheral DNA samples from discordant MZ twin pairs. Our data suggest that differences in DNA methylation associated with childhood asthma which persists into early adulthood are distinct from those associated with asthma which remits.
哮喘是儿童中最常见的慢性炎症性疾病。哮喘病理的病因复杂且高度异质性，涉及遗传和环境风险因素之间的相互作用，据推测这涉及表观遗传过程。我们的目的是探讨从环境风险（E-Risk）纵向双胞胎研究中招募的同卵（MZ）双胞胎对中，儿童期甲基化组变异是否与哮喘症状不一致相关。我们还旨在确定与儿童期发生并持续到成年早期的哮喘相关的DNA甲基化差异，因为这些差异可能代表有用的预后生物标志物。
我们检查了从37对10岁时哮喘症状不一致的MZ双胞胎对收集的颊细胞样本中的全基因组DNA甲基化模式。单个CpG位点的DNA甲基化在不一致的MZ双胞胎对中表现出显著变异性，排名最高的名义上显著的差异甲基化位点（DMP）位于HGSNAT基因中。我们通过评估18岁时哮喘仍持续不一致的MZ双胞胎对亚组中的DNA甲基化差异来分层分析。与持续性哮喘相关的排名最高的名义上显著的DMP位于HLX基因附近，该基因先前已被认为与儿童哮喘有关。
我们在不一致的MZ双胞胎对的外周DNA样本中鉴定出与儿童哮喘相关的DNA甲基化差异。我们的数据表明，与持续到成年早期的儿童哮喘相关的DNA甲基化差异与缓解的哮喘相关的差异不同。
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