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. 2018;13(2):163-172.
doi: 10.1080/15592294.2017.1287654. Epub 2018 Mar 6.

Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples

Xiumei Hong  1 , Ben Sherwood  2 , Christine Ladd-Acosta  3 , Shouneng Peng  4 , Hongkai Ji  2 , Ke Hao  4 , Irina Burd  5 , Tami R Bartell  6 , Guoying Wang  1 , Hui-Ju Tsai  7   8 , Xin Liu  8   9 , Yuelong Ji  1 , Anastacia Wahl  10 , Deanna Caruso  1 , Aviva Lee-Parritz  11 , Barry Zuckerman  10 , Xiaobin Wang  1   12
Affiliations

Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples

Xiumei Hong et al. Epigenetics. 2018.

Abstract

Preterm birth (PTB) affects one in six Black babies in the United States. 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 HumanMethylation450 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 medically-indicated PTB, 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.

Keywords: DNA methylation; epigenome-wide associations; maternal blood; spontaneous preterm birth.

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Figures

Figure 1.
Figure 1.
Manhattan plot for the genome-wide DNA methylation associations with early spontaneous preterm birth in 290 Black women from the Boston Birth Cohort. The dashed line represents false discovery rate = 5%.
Figure 2.
Figure 2.
The distribution of DNA methylation levels at the two validated sites in both the discovery and replication Black maternal samples from the Boston Birth Cohort, stratified by term vs. preterm status of the neonates. TB: term birth; sPTB: spontaneous PTB; mPTB: medically-indicated PTB. P values shown in the figure were calculated using the regression models to indicate a significant DNAm difference between mothers in each PTB subgroup and mothers with TBs.
Figure 3.
Figure 3.
The maternal-cord blood DNA methylation correlation at cg03915055 and cg06804705, and cord blood DNA methylation difference at these two sites between term and PTB neonates. TB: term birth; sPTB: spontaneous PTB; mPTB: medically-induced PTB.
Figure 4.
Figure 4.
Distributions of DNA methylation at cg03915055 and cg06804705 in mothers from the discovery sample, stratified by TB/PTB status combined with the existence of pregnancy complications. TB: term birth; sPTB: spontaneous PTB; DM/GDM: diabetes and gestational diabetes.
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References

    1. Callaghan WM, MacDorman MF, Rasmussen SA, et al. The contribution of preterm birth to infant mortality rates in the United States. Pediatrics. 2006;118:1566–1573. doi: 10.1542/peds.2006-0860. PMID:17015548 - DOI - PubMed
    1. Lopez-Serra P, Esteller M. DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene. 2012;31:1609–1622. doi: 10.1038/onc.2011.354. PMID:21860412 - DOI - PMC - PubMed
    1. Laurent L, Wong E, Li G, et al. Dynamic changes in the human methylome during differentiation. Genome Res. 2010;20:320–331. doi: 10.1101/gr.101907.109. PMID:20133333 - DOI - PMC - PubMed
    1. Maunakea AK, Nagarajan RP, Bilenky M, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466:253–257. doi: 10.1038/nature09165. PMID:20613842 - DOI - PMC - PubMed
    1. Heyn H, Esteller M. DNA methylation profiling in the clinic: applications and challenges. Nat Rev Gene. 2012;13:679–692. doi: 10.1038/nrg3270. PMID:22945394 - DOI - PubMed

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