An epigenetic clock for gestational age at birth based on blood methylation data

Abstract

BackgroundGestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth.ResultsWe find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry.ConclusionsDNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1068-z) contains supplementary material, which is available to authorized users.

The Epigenetic Clock at Birth: Associations With Maternal Antenatal Depression and Child Psychiatric Problems

“…DNAm GA was calculated as described elsewhere, 10 based on the methylation profile of 148 selected CpG sites. Chronological GA was based on ultrasound scans, and epigenetic GA was calculated as the arithmetic difference between DNAm GA and chronological GA and adjusted for chronological GA.…”

“…9 These predictors are, however, not well suited for epigenetic age estimation at birth, because their correlation with chronological GA is nearly 0. 9 A recent study generated a novel epigenetic GA biomarker based on fetal umbilical cord blood or newborn blood spots, 10 which showed a high correlation with ultrasound-based GA. 10 This study demonstrated that lower epigenetic GA (lower DNAm GA than chronological GA) at birth was associated with maternal socioeconomic disadvantage and low birth weight. We have extended these analyses by showing that lower epigenetic GA was associated with maternal insulin-treated gestational diabetes mellitus in a previous pregnancy and in Sjögren syndrome, and higher epigenetic GA with a maternal age of more than 40 years at delivery, neonate’s lower 1-minute Apgar score, and female sex.…”

Tracing human stem cell lineage during development using DNA methylation

“…Horvath's DNA methylation age was calculated using the agep function in the Cold Spring Harbor Laboratory Press on April 27, 2019 -Published by genome.cshlp.org Downloaded from wateRmelon R-package (Pidsley et al 2013). For newborns, we estimated the Knight's DNA methylation gestational age (Knight et al 2016). The pooled dataset was normalized using Funnorm (Fortin et al 2014).…”

“…We used five independent datasets to evaluate the classification area under the ROC (AUROC) curve of the FCO signature and the stability of the FCO estimations (Supplemental Methods S1): UCB GSE80310 (Knight et al 2016), GSE74738 (Hanna et al 2016), GSE54399 (Montoya-Williams et al 2017, GSE79056 (Knight et Cold Spring Harbor Laboratory Press on April 27, 2019 -Published by genome.cshlp.org Downloaded from 20 al. 2016), GSE62924 (Rojas et al 2015).…”

Relationship between Epigenetic Maturity and Respiratory Morbidity in Preterm Infants

“…15 We have recently developed a method to predict gestational age at birth using DNAm at 148 CpG sites across the genome. 16 DNAm gestational age is highly correlated with clinically estimated gestational age. The residual between DNAm age and clinical gestational age, known as gestational age acceleration, has previously been associated with birth weight, which may reflect developmental maturity.…”