Sex-specific associations of asthma acquisition with changes in DNA methylation during adolescence.
Sex-specific associations of asthma acquisition with changes in DNA methylation during adolescence.
复制标题
青少年期哮喘发病与DNA甲基化变化的性别特异性相关性
DOI：
10.1111/cea.13776
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
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从青春期前到青春期后哮喘状态变化的性别差异所涉及的潜在生物学机制尚不清楚。DNA甲基化（DNAm）已被证明与哮喘风险有关。我们假设，从青春期前到青春期后获得哮喘与此期间哮喘相关的胞嘧啶-磷酸-鸟嘌呤（CpG）位点的dna变化有关，并且这种关联具有性别特异性。研究对象来自10岁和18岁的怀特岛出生队列（IOWBC），血液中含有dna（124名女性，151名男性）。使用训练测试方法，确定了与哮喘相关的全表观基因组CpGs。在哮喘相关CpGs中，使用Logistic回归来检验10至18岁之间DNAm变化与哮喘获得的性别特异性关联。使用ALSPAC出生队列进行独立复制。为了评估鉴定的CpGs的功能相关性，我们评估了血液中dna与基因表达的关系。我们确定了535个CpGs可能与哮喘相关。在IOWBC的535个CpGs中，有13个发现了DNAm变化和性别对青少年哮喘获得的显著交互作用（p值<1.0 × 10−）。在复制队列中，在13个CpGs中有10个观察到一致的相互作用效应。在这10个CpGs中有7个，在两个队列中，在青春期观察到相反的DNAm变化。在这两个队列中，位于与哮喘相关的IFRD1上的cg20891917对哮喘转变表现出强烈的性别特异性影响（两个队列的p值均< 0.01）。在哮喘相关CpGs中，从青春期前到青春期后，哮喘获得的性别逆转与DNAm（男性与女性）的相反变化有关。这些CpGs是青春期性别特异性哮喘获得的潜在生物标志物。
Underlying biological mechanisms involved in sex differences in asthma status changes from pre- to post-adolescence are unclear. DNA methylation (DNAm) has been shown to be associated with the risk of asthma. We hypothesized that asthma acquisition from pre- to post-adolescence was associated with changes in DNAm during this period at asthma-associated cytosine-phosphate-guanine (CpG) sites and such an association was sex-specific. Subjects from the Isle of Wight birth cohort (IOWBC) with DNAm in blood at ages 10 and 18 years (n = 124 females, 151 males) were studied. Using a training-testing approach, epigenome-wide CpGs associated with asthma were identified. Logistic regression was used to examine sex-specific associations of DNAm changes with asthma acquisition between ages 10 and 18 at asthma-associated CpGs. The ALSPAC birth cohort was used for independent replication. To assess functional relevance of identified CpGs, association of DNAm with gene expression in blood was assessed. We identified 535 CpGs potentially associated with asthma. Significant interaction effects of DNAm changes and sex on asthma acquisition in adolescence were found at 13 of the 535 CpGs in IOWBC (P-values <1.0 × 10−). In the replication cohort, consistent interaction effects were observed at 10 of the 13 CpGs. At 7 of these 10 CpGs, opposite DNAm changes across adolescence were observed between sexes in both cohorts. In both cohorts, cg20891917, located on IFRD1 linked to asthma, shows strong sex-specific effects on asthma transition (P-values <.01 in both cohorts). Gender reversal in asthma acquisition is associated with opposite changes in DNAm (males vs females) from pre- to post-adolescence at asthma-associated CpGs. These CpGs are potential biomarkers of sex-specific asthma acquisition in adolescence.
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影响因子：
5.7
作者：
Arathimos R;Suderman M;Sharp GC;Burrows K;Granell R;Tilling K;Gaunt TR;Henderson J;Ring S;Richmond RC;Relton CL
通讯作者：
Relton CL
影响因子：
3.1
作者：
Machin M;Amaral AF;Wielscher M;Rezwan FI;Imboden M;Jarvelin MR;Adcock IM;Probst-Hensch N;Holloway JW;Jarvis DL;ALEC study
通讯作者：
ALEC study
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
9.8
作者：
Joubert, Bonnie R.;Felix, Janine F.;London, Stephanie J.
通讯作者：
London, Stephanie J.
影响因子：
3.7
作者：
Gunawardhana, Lakshitha P.;Gibson, Peter G.;Baines, Katherine J.
通讯作者：
Baines, Katherine J.