BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA methylation.
BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA methylation.
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DOI：
10.1186/s13223-021-00575-w
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发表时间：
2021-07-23
期刊：
影响因子：
--
通讯作者：
Holloway JW
中科院分区：
文献类型：
--
作者：
Rathod R;Zhang H;Karmaus W;Ewart S;Kadalayil L;Relton C;Ring S;Arshad SH;Holloway JW
体重指数（BMI）与哮喘相关，但BMI时间模式与哮喘发病率的关系尚不清楚。先前的研究表明DNA甲基化（DNAm）与哮喘状态相关，DNAm的变化是BMI变化的结果。本研究评估了儿童时期BMI轨迹对青年期哮喘发病率的直接和间接（通过DNAm）影响。来自怀特岛（IoW）出生队列的数据被纳入分析。基于组的轨迹模型被应用于推断1至10岁的潜在BMI轨迹。应用R包ttscreening来鉴定与BMI轨迹相关的10岁时差异甲基化CpG，按性别分层。Logistic回归用于进一步排除10岁时DNA m与18岁时哮喘发病率无关的CpG。通过路径分析发现的CpG介导了IoW队列中BMI轨迹与哮喘发病率的相关性，并在一个独立的队列中进行了进一步测试，即雅芳儿童和父母纵向研究（ALSPAC）。确定了两个BMI轨迹（高vs正常）。在442，474个CpG位点中，男性中159个CpG位点和女性中212个CpG位点的DNAm可能与BMI轨迹相关。评估其与哮喘发病率的相关性，发现男性中有9个CpG，女性中有6个CpG。在这15个CpG中的4个处的DNAm显示统计学显著的介导作用（p值< 0.05）。在4个CpG中的两个（cg 23632109和cg 10817500）处，DNAm完全介导了这种关联（即，仅鉴定出统计学上显著的间接影响）。在ALSPAC队列中，在所有四个CpG上，观察到与IoW队列中发现的介导效应方向相同的介导效应，尽管统计学上不显着。儿童期BMI轨迹与青年期哮喘发病率的相关性可能由DNAm介导。在线版本包含补充材料，可通过10.1186/s13223-021-00575-w获得。
Body mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood. Data from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC). Two BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant. The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm. The online version contains supplementary material available at 10.1186/s13223-021-00575-w.
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影响因子：
3.5
作者：
Ding, Xu;Zheng, Dongyi;Qi, Kemin
通讯作者：
Qi, Kemin
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：
7.6
作者：
BARON, RM;KENNY, DA
通讯作者：
KENNY, DA
影响因子：
3.5
作者：
Farahi N;Paige E;Balla J;Prudence E;Ferreira RC;Southwood M;Appleby SL;Bakke P;Gulsvik A;Litonjua AA;Sparrow D;Silverman EK;Cho MH;Danesh J;Paul DS;Freitag DF;Chilvers ER
通讯作者：
Chilvers ER
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W