基于母体血液白细胞中 DNA 甲基化的全基因组关联研究与妊娠期间 BMI 和妊娠体重增加的关系。
Epigenome-wide association study of DNA methylation in maternal blood leukocytes with BMI in pregnancy and gestational weight gain.
机构信息
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
出版信息
Int J Obes (Lond). 2024 Apr;48(4):584-593. doi: 10.1038/s41366-024-01458-x. Epub 2024 Jan 13.
OBJECTIVES
We aimed to discover CpG sites with differential DNA methylation in peripheral blood leukocytes associated with body mass index (BMI) in pregnancy and gestational weight gain (GWG) in women of European and South Asian ancestry. Furthermore, we aimed to investigate how the identified sites were associated with methylation quantitative trait loci, gene ontology, and cardiometabolic parameters.
METHODS
In the Epigenetics in pregnancy (EPIPREG) sample we quantified maternal DNA methylation in peripheral blood leukocytes in gestational week 28 with Illumina's MethylationEPIC BeadChip. In women with European (n = 303) and South Asian (n = 164) ancestry, we performed an epigenome-wide association study of BMI in gestational week 28 and GWG between gestational weeks 15 and 28 using a meta-analysis approach. Replication was performed in the Norwegian Mother, Father, and Child Cohort Study, the Study of Assisted Reproductive Technologies (MoBa-START) (n = 877, mainly European/Norwegian).
RESULTS
We identified one CpG site significantly associated with GWG (p 5.8 × 10-8) and five CpG sites associated with BMI at gestational week 28 (p from 4.0 × 10-8 to 2.1 × 10-10). Of these, we were able to replicate three in MoBa-START; cg02786370, cg19758958 and cg10472537. Two sites are located in genes previously associated with blood pressure and BMI. DNA methylation at the three replicated CpG sites were associated with levels of blood pressure, lipids and glucose in EPIPREG (p from 1.2 × 10 to 0.04).
CONCLUSIONS
We identified five CpG sites associated with BMI at gestational week 28, and one with GWG. Three of the sites were replicated in an independent cohort. Several genetic variants were associated with DNA methylation at cg02786379 and cg16733643 suggesting a genetic component influencing differential methylation. The identified CpG sites were associated with cardiometabolic traits.
GOV REGISTRATION NO
Not applicable.
目的
我们旨在发现与欧洲和南亚血统孕妇妊娠 28 周时体重指数（BMI）和妊娠期间体重增加（GWG）相关的外周血白细胞中差异 DNA 甲基化的 CpG 位点。此外，我们旨在研究鉴定出的位点与甲基化数量性状基因座、基因本体和心血管代谢参数的关系。
方法
在 Epigenetics in pregnancy (EPIPREG) 研究中，我们使用 Illumina 的 MethylationEPIC BeadChip 量化了妊娠 28 周时孕妇外周血白细胞中的 DNA 甲基化。在具有欧洲（n=303）和南亚（n=164）血统的女性中，我们使用荟萃分析方法对妊娠 28 周时的 BMI 和妊娠 15-28 周时的 GWG 进行了全基因组关联研究。在挪威母亲、父亲和儿童队列研究（MoBa-START）（n=877，主要为欧洲/挪威）中进行了复制。
结果
我们鉴定出一个与 GWG 显著相关的 CpG 位点（p 5.8×10-8）和五个与妊娠 28 周时 BMI 相关的 CpG 位点（p 从 4.0×10-8 到 2.1×10-10）。在这些位点中，我们能够在 MoBa-START 中复制三个：cg02786370、cg19758958 和 cg10472537。两个位点位于先前与血压和 BMI 相关的基因中。在 EPIPREG 中，三个复制 CpG 位点的 DNA 甲基化与血压、血脂和血糖水平相关（p 从 1.2×10-8 到 0.04）。
结论
我们鉴定出五个与妊娠 28 周时 BMI 相关的 CpG 位点，一个与 GWG 相关的 CpG 位点。其中三个位点在独立队列中得到了复制。一些遗传变异与 cg02786379 和 cg16733643 处的 DNA 甲基化相关，表明遗传因素影响差异甲基化。鉴定出的 CpG 位点与心血管代谢特征相关。
政府注册号
不适用。
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