Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA, 15261, USA.
Division of Internal Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Reprod Sci. 2021 Dec;28(12):3519-3528. doi: 10.1007/s43032-021-00575-6. Epub 2021 Apr 20.
Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. Chronological age and race are associated with preeclampsia, but the role of these factors is not entirely understood. We hypothesized that DNA methylation age, a measure of biological age, would be higher in individuals with preeclampsia than in individuals with normotensive pregnancy and that DNA methylation age would differ by race across pregnancy. This was a longitudinal, exploratory study of 56 pregnant individuals (n = 28 preeclampsia cases and n = 28 normotensive controls). Genome-wide DNA methylation data were generated from trimester-specific peripheral blood samples. DNA methylation age was estimated using the "Improved Precision" clock, and ∆age, the difference between DNA methylation age and chronological age, was computed. DNA methylation age was compared with chronological age using Pearson correlations. The relationships between ∆age and preeclampsia status, self-reported race, and covariates were tested using multiple linear regression and performed both with and without consideration of cell-type heterogeneity. We observed strong correlation between chronological age and DNA methylation age across pregnancy, with significantly stronger correlation observed in White participants than in Black participants. We observed no association between ∆age and preeclampsia status. However, ∆age was higher in participants with higher pre-pregnancy body mass index in trimester 1 and lower in Black participants than in White participants in trimesters 2 and 3. Observations were largely consistent when controlling for cell-type heterogeneity. Our findings in a small sample support the need for additional studies to investigate the relationship between race and biological age, which could provide further insight into racial disparities across pregnancy. However, this study does not support an association between ∆age and preeclampsia status.
子痫前期是孕产妇和新生儿发病率和死亡率的主要原因。年龄和种族与子痫前期有关，但这些因素的作用尚不完全清楚。我们假设，与正常妊娠相比，患有子痫前期的个体的 DNA 甲基化年龄（衡量生物年龄的指标）更高，并且 DNA 甲基化年龄在妊娠期间会因种族而异。这是一项对 56 名孕妇（n=28 例子痫前期病例和 n=28 例正常血压对照组）进行的纵向、探索性研究。从特定于妊娠阶段的外周血样本中生成全基因组 DNA 甲基化数据。使用“改进精度”时钟估计 DNA 甲基化年龄，并计算 DNA 甲基化年龄与实际年龄之间的差异 ∆age。使用 Pearson 相关系数比较 DNA 甲基化年龄与实际年龄。使用多元线性回归测试 ∆age 与子痫前期状态、自我报告的种族以及协变量之间的关系，并在考虑和不考虑细胞类型异质性的情况下分别进行测试。我们观察到整个孕期中，实际年龄与 DNA 甲基化年龄之间存在很强的相关性，在白种参与者中观察到的相关性明显强于在黑种参与者中观察到的相关性。我们没有观察到 ∆age 与子痫前期状态之间存在关联。然而，在第 1 个孕期中，具有较高的孕前体重指数的参与者的 ∆age 较高，而在第 2 和第 3 个孕期中，黑种参与者的 ∆age 低于白种参与者。当控制细胞类型异质性时，观察结果基本一致。我们在小样本中的发现支持需要进行更多的研究来调查种族与生物年龄之间的关系，这可能为妊娠期间的种族差异提供进一步的见解。然而，这项研究并不支持 ∆age 与子痫前期状态之间存在关联。
