Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, 23220, USA.
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, 23220, USA.
Sci Rep. 2021 Jul 29;11(1):15440. doi: 10.1038/s41598-021-94281-7.
Maternal age is an established predictor of preterm birth independent of other recognized risk factors. The use of chronological age makes the assumption that individuals age at a similar rate. Therefore, it does not capture interindividual differences that may exist due to genetic background and environmental exposures. As a result, there is a need to identify biomarkers that more closely index the rate of cellular aging. One potential candidate is biological age (BA) estimated by the DNA methylome. This study investigated whether maternal BA, estimated in either early and/or late pregnancy, predicts gestational age at birth. BA was estimated from a genome-wide DNA methylation platform using the Horvath algorithm. Linear regression methods assessed the relationship between BA and pregnancy outcomes, including gestational age at birth and prenatal perceived stress, in a primary and replication cohort. Prenatal BA estimates from early pregnancy explained variance in gestational age at birth above and beyond the influence of other recognized preterm birth risk factors. Sensitivity analyses indicated that this signal was driven primarily by self-identified African American participants. This predictive relationship was sensitive to small variations in the BA estimation algorithm. Benefits and limitations of using BA in translational research and clinical applications for preterm birth are considered.
母亲的年龄是预测早产的一个既定因素，独立于其他公认的风险因素。使用实际年龄的假设是，个体的衰老速度相似。因此，它无法捕捉到由于遗传背景和环境暴露而可能存在的个体差异。因此，有必要确定更能准确反映细胞衰老速度的生物标志物。一个潜在的候选者是通过 DNA 甲基化组学估计的生物年龄 (BA)。本研究调查了在早期和/或晚期妊娠中估计的母体 BA 是否预测出生时的胎龄。BA 是使用 Horvath 算法从全基因组 DNA 甲基化平台上估计的。线性回归方法评估了 BA 与妊娠结局（包括出生时的胎龄和产前感知压力）之间的关系，该研究在一个原始队列和一个复制队列中进行。早期妊娠的产前 BA 估计值解释了出生时胎龄的变异性，超过了其他公认的早产风险因素的影响。敏感性分析表明，这一信号主要是由自我认定的非裔美国参与者驱动的。这种预测关系对 BA 估计算法的微小变化很敏感。考虑了在早产的转化研究和临床应用中使用 BA 的益处和局限性。
