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Genome-wide DNA Methylation Associations with Spontaneous Preterm Birth in US Blacks: Findings in Maternal and Cord Blood Samples

TitleGenome-wide DNA Methylation Associations with Spontaneous Preterm Birth in US Blacks: Findings in Maternal and Cord Blood Samples
Publication TypeJournal Article
Year of Publication2017
AuthorsHong, X, Sherwood, B, Ladd-Acosta, C, Peng, S, Ji, H, Hao, K, Burd, I, Bartell, TR, Wang, G, Tsai, HJ, Liu, X, Ji, Y, Wahl, A, Caruso, D, Lee-Parritz, A, Zuckerman, B, Wang, X
JournalEpigenetics
Date PublishedFeb 06
ISBN Number1559-2294
Accession Number28165855
KeywordsDNA methylation, Epigenome-wide associations, maternal blood, Spontaneous preterm birth
Abstract

Preterm birth (PTB) affects one in six U.S. Black babies. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort. DNAm in maternal blood and/or cord blood was measured using the Illumina HumanMethylation 450K BeadChip. We identified 45 DNAm loci in maternal blood associated with early sPTB, with a false discovery rate (FDR) <5%. Replication analyses confirmed sPTB associations for cg03915055 and cg06804705, located in the promoter regions of the CYTIP and LINC00114 genes, respectively. Both loci had comparable associations with early sPTB and early mPTB, but attenuated associations with late sPTB. These associations could not be explained by cell composition, gestational complications, and/or nearby maternal genetic variants. Analyses in the newborns of the 110 Black women showed that cord blood methylation levels at both loci had no associations with PTB. The findings from this study underscore the role of maternal DNAm in PTB risk, and provide a set of maternal loci that may serve as biomarkers for PTB. Longitudinal studies are needed to clarify temporal relationships between maternal DNAm and PTB risk.