MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Nat Commun. 2019 Apr 23;10(1):1893. doi: 10.1038/s41467-019-09671-3.
Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P < 1.06 x 10). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10) and BMI in pregnancy (3/914, p = 1.13x10), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
出生体重与整个生命过程中的健康结果有关，DNA 甲基化可能是其潜在机制。在这项对来自妊娠和儿童表观遗传学联盟的 24 个出生队列的 8825 名新生儿的全基因组关联研究的表观基因组学荟萃分析中，我们发现新生儿血液中的 DNA 甲基化与 914 个部位的出生体重相关，每增加 10%的甲基化，出生体重的差异范围为-183 至 178 克（P < 1.06 x 10）。在 7278 名参与者的额外分析中，在儿童期和青春期也观察到与出生体重相关的差异甲基化<1.3%，但在成年期没有观察到。与出生体重相关的 CpG 与一些先前报道与母亲吸烟（55/914，p = 6.12 x 10）和妊娠期间 BMI（3/914，p = 1.13 x 10）相关的 Bonferroni 显著 CpG 重叠，但与妊娠期间叶酸水平相关的 CpG 不重叠。我们观察到的关联是因果关系还是由混杂因素或胎儿生长影响 DNA 甲基化（即反向因果关系）解释，需要进一步研究。
