Birthweight DNA methylation signatures in infant saliva.
Birthweight DNA methylation signatures in infant saliva.
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DOI：
10.1186/s13148-021-01053-1
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发表时间：
2021-03-19
影响因子：
5.7
通讯作者：
Richiardi L
中科院分区：
文献类型：
--
作者：
Moccia C;Popovic M;Isaevska E;Fiano V;Trevisan M;Rusconi F;Polidoro S;Richiardi L
低出生体重一再与长期不利的健康结果和许多非传染性疾病有关。我们的目的是查找PACE联盟在婴儿唾液中鉴定的与脐带血出生体重相关的CpG位点，并探索出生体重的唾液特异性DNA甲基化特征。使用Infinium HumanMethylation 450 K阵列评估了从NINFEA出生队列中平均年龄为10.8（范围7-17）个月的儿童收集的135份唾液样本中的DNA甲基化。在探索性EWAS分析和婴儿唾液中PACE结果的查找中，使用稳健的线性回归模型进行出生体重和DNA甲基化变化之间的关联分析。当在婴儿唾液中分析时，PACE联盟确定的脐带血出生体重相关CpG均与出生体重无关。在唾液EWAS分析中，考虑到错误发现率p值< 0.05，出生体重作为连续变量与44个CpG位点的DNA甲基化相关;出生小于胎龄（SGA，根据WHO参考图表，出生体重小于胎龄的第10百分位数）与44个CpG位点的DNA甲基化相关，两个分析之间只有一个重叠的CpG。尽管在CpG水平上与PACE结果没有重叠，但在PACE联盟中，两个最高唾液出生体重CpG定位在与出生体重相关的基因上，具有相同的作用方向（MACROD 1和RPTOR）。我们的研究提供了10个月左右儿童的出生体重和SGA表观遗传唾液特征的指示。脐带血中的DNA甲基化特征可能无法与大约10个月大时的唾液DNA甲基化特征进行比较，这表明出生体重表观遗传标记可能具有时间和组织特异性。在线版本包含补充材料，可通过10.1186/s13148-021-01053-1获得。
Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific. The online version contains supplementary material available at 10.1186/s13148-021-01053-1.
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