DNA methylation signatures in cord blood associated with birthweight are enriched for dmCpGs previously associated with maternal hypertension or pre-eclampsia, smoking and folic acid intake.
DNA methylation signatures in cord blood associated with birthweight are enriched for dmCpGs previously associated with maternal hypertension or pre-eclampsia, smoking and folic acid intake.
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DOI：
10.1080/15592294.2021.1908706
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发表时间：
2022-04
期刊：
影响因子：
3.7
通讯作者：
UPBEAT Consortium/EpiGen Consortium
中科院分区：
文献类型：
--
作者：
Antoun E;Titcombe P;Dalrymple K;Kitaba NT;Barton SJ;Flynn A;Murray R;Garratt ES;Seed PT;White SL;Cooper C;Inskip HM;Hanson M;Poston L;Godfrey KM;Lillycrop KA;UPBEAT Consortium/EpiGen Consortium
许多流行病学研究将低出生体重与晚年非传染性疾病（NCD）风险增加联系起来，表观遗传过程被认为是一种潜在机制。在这里，我们试图在个体CpG和基因组区域水平上确定与出生体重相关的新生儿甲基化变化，以及出生体重相关的甲基化特征是否与特定的母体因素相关。使用Illumina人类甲基化EPIC阵列，我们分别评估了来自英国孕妇更好饮食和活动试验和南安普顿妇女调查的557名和483名婴儿的脐带血中的DNA甲基化。校正胎龄和其他协变量后，一项表观全基因组关联研究确定了2911个（FDR≤0.05）和236个（Bonferroni校正p ≤ 6.45×10−8）差异甲基化CpG（dmCpG），以及1230个差异甲基化区域（DMR）（Stouffer ≤0.05）与出生体重相关。与出生体重相关的最高dmCpG位于同源盒端粒结合蛋白1（HMBOX 1）基因内，甲基化每增加10%，出生体重减少195 g（95%CI：-241，-149 g），而最高DMR位于促肾上腺皮质激素释放肽结合蛋白（CRHBP）的启动子内。此外，与出生体重相关的dmCpG富集了先前与妊娠期高血压/先兆子痫（14.51%，p = 1.37×10−255），母亲吸烟（7.71%，p = 1.50 × 10−57）和妊娠期间母亲血浆叶酸水平（0.33%，p = 0.029）相关的dmCpG。识别出生体重相关的甲基化标志物，特别是与特定妊娠并发症和暴露相关的甲基化标志物，可以深入了解影响出生体重的发育途径，并建议替代标志物来识别不良产前暴露，以便对后期NCD风险的个体进行分层。
Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human Methylation EPIC array, we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women’s Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p ≤ 6.45×10−8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195 g (95%CI: −241, −149 g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin-releasing hormone-binding protein (CRHBP). Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p = 1.37×10−255), maternal smoking (7.71%, p = 1.50 x 10−57) and maternal plasma folate levels during pregnancy (0.33%, p = 0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.
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