胎儿发育和出生结局的妊娠期 DNA 甲基化年龄标志物：来自波士顿出生队列的研究结果。

Gestational DNA methylation age as a marker for fetal development and birth outcomes: findings from the Boston Birth Cohort.

机构信息

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.

Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

出版信息

Clin Epigenetics. 2024 Aug 20;16(1):110. doi: 10.1186/s13148-024-01714-x.

DOI:10.1186/s13148-024-01714-x

PMID:39164769

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11334360/

Abstract

BACKGROUND

Gestational DNA methylation age (GAmAge) has been developed and validated in European ancestry samples. Its applicability to other ethnicities and associations with fetal stress and newborn phenotypes such as inflammation markers are still to be determined. This study aims to examine the applicability of GAmAge developed from cord blood samples of European decedents to a racially diverse birth cohort, and associations with newborn phenotypes.

METHODS

GAmAge based on 176 CpGs (Haftorn GAmAge) was calculated for 940 children from a US predominantly urban, low-income, multiethnic birth cohort. Cord blood DNA methylation was profiled by Illumina EPIC array. Newborn phenotypes included anthropometric measurements and, for a subset of newborns (N = 194), twenty-seven cord blood inflammatory markers (sandwich immunoassays).

RESULTS

GAmAge had a stronger correlation with GEAA in boys (r = 0.89, 95% confidence interval (CI) [0.87,0.91]) compared with girls (r = 0.83, 95% CI [0.80,0.86]), and was stronger among extremely preterm to very preterm babies (r = 0.91, 95% CI [0.81,0.96]), compared with moderate (r = 0.48, 95% CI [0.34,0.60]) and term babies (r = 0.58, 95% CI [0.53,0.63]). Among White newborns (N = 51), the correlation between GAmAge vs. GEAA was slightly stronger (r = 0.89, 95% CI [0.82,0.94]) compared with Black/African American newborns (N = 668; r = 0.87, 95% CI [0.85,0.89]) or Hispanic (N = 221; r = 0.79, 95% CI [0.74,0.84]). Adjusting for GEAA and sex, GAmAge was associated with anthropometric measurements, cord blood brain-derived neurotrophic factor (BDNF), and monocyte chemoattractant protein-1 (MCP-1) (p < 0.05 for all).

CONCLUSIONS

GAmAge estimation is robust across different populations and racial/ethnic subgroups. GAmAge may be utilized as a proxy for GEAA and for assessing fetus development, indicated by inflammatory state and birth outcomes.

摘要

背景

Gestational DNA methylation age（GAmAge）已在欧洲血统样本中开发和验证。其在其他种族中的适用性以及与胎儿应激和新生儿表型（如炎症标志物）的关系仍有待确定。本研究旨在检验基于欧洲死者脐带血样本开发的 GAmAge 应用于美国以城市为主、低收入、多种族出生队列的适用性，并探讨其与新生儿表型的关系。

方法

本研究使用 Illumina EPIC 芯片对来自美国以城市为主、低收入、多种族出生队列的 940 名儿童的脐带血 DNA 甲基化进行了分析，计算了基于 176 个 CpG 位点（Haftorn GAmAge）的 GAmAge。新生儿表型包括人体测量学指标，对于一部分新生儿（N=194），还包括 27 个脐带血炎症标志物（夹心免疫测定法）。

结果

GAmAge 在男孩中的相关性（r=0.89，95%置信区间[0.87，0.91]）强于女孩（r=0.83，95%置信区间[0.80，0.86]），在极早产儿至非常早产儿中（r=0.91，95%置信区间[0.81，0.96]）的相关性强于中度早产儿（r=0.48，95%置信区间[0.34，0.60]）和足月产儿（r=0.58，95%置信区间[0.53，0.63]）。在白人新生儿中（N=51），GAmAge 与 GEAA 的相关性略强（r=0.89，95%置信区间[0.82，0.94]），而在黑人/非裔美国人新生儿中（N=668）和西班牙裔新生儿中（N=221），相关性分别为 0.87（95%置信区间[0.85，0.89]）和 0.79（95%置信区间[0.74，0.84]）。在调整了 GEAA 和性别后，GAmAge 与人体测量学指标、脐带血脑源性神经营养因子（BDNF）和单核细胞趋化蛋白-1（MCP-1）相关（所有 p 值均<0.05）。