The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Room Na-2918, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Genome Med. 2020 Nov 25;12(1):105. doi: 10.1186/s13073-020-00810-w.
DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.
We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.
DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P = 1; childhood P = 2.00 × 10; adolescence P = 2.10 × 10).
There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.
已有研究表明，DNA 甲基化与成年后的肥胖有关。然而，儿童和青少年时期是否存在类似的 DNA 甲基化模式与 BMI 相关，目前还知之甚少。在更年轻时深入了解这种关系，可能对未来预防肥胖及其相关特征具有重要意义。
我们使用横断面和纵向模型，分别在儿童和青少年时期的脐带血和全血中，检测 DNA 甲基化与 2 至 18 岁之间 BMI 的相关性。我们对包括 23 项研究的 4133 名儿童在内的全基因组关联研究进行荟萃分析。我们还检验了先前在儿童和成人中报道的研究结果与我们分析结果的重叠情况，并计算了富集程度。
在三个不同年龄段（cg05937453、cg25212453 和 cg10040131）的三个 CpG 位点（cg05937453、cg25212453 和 cg10040131），其 DNA 甲基化与 BMI 相关，达到 Bonferroni 显著性水平（P<1.06×10），每增加 10%的甲基化，BMI 分别高出 0.96 个标准差评分（SE 0.17）、0.32 个标准差评分（SE 0.06）和 0.32 个 BMI 标准差评分（SE 0.06）。在横断面儿童模型中，9 个额外的 CpG 与 BMI 相关，达到假发现率显著性水平。在我们的分析中，随着儿童和青少年年龄的增长，先前与成人 BMI 相关的 187 个 CpG 位点的 DNA 甲基化关联强度也随之增强。此外，在成年人和儿童青少年中，这些 CpG 效应估计值之间的相关系数也有所增加。在每个年龄段的主要发现中，我们观察到先前在成人中发现的 CpG 位点的富集程度增加（出生时 P=1；儿童时 P=2.00×10；青春期时 P=2.10×10）。
DNA 甲基化与儿童和青少年 BMI 仅有轻微关联。随着参与者在儿童和青少年时期年龄的增长，我们观察到与与成人 BMI 相关的改变的 DNA 甲基化位点的重叠程度增加。这些发现可能与 DNA 甲基化差异主要是肥胖的结果而不是原因的假说相符。
