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Epigenetics. 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.

Author information

1
a Department of Population , Family and Reproductive Health , Center on the Early Life Origins of Disease , Johns Hopkins University Bloomberg School of Public Health , Baltimore , MD , USA.
2
b Department of Biostatistics , Johns Hopkins University Bloomberg School of Public Health, Baltimore , MD , USA.
3
c Department of Epidemiology, The Wendy Klag Center for Autism and Developmental Disabilities , Johns Hopkins Bloomberg School of Public Health , Baltimore , MD 21205.
4
d Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York , NY , 10029 , USA.
5
e Integrated Research Center for Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
6
f Mary Ann & J. Milburn Smith Child Health Research Program , Stanley Manne Children's Research Institute , Ann & Robert H. Lurie Children's Hospital of Chicago , Chicago , IL , 60611 , USA.
7
g Division of Biostatistics and Bioinformatics , Institute of Population Health Sciences , National Health Research Institutes , Zhunan , Taiwan 350.
8
h Department of Pediatrics, Feinberg School of Medicine , Northwestern University , Chicago , IL , 60611 , USA.
9
i Key Laboratory of Genomic and Precision Medicine , Beijing Institute of Genomics , Chinese Academy of Sciences , Beijing , 100101 , China.
10
j Department of Pediatrics , Boston University School of Medicine and Boston Medical Center , Boston , MA, USA.
11
k Department of Obstetrics and Gynecology , Boston University School of Medicine , Boston , MA, USA.
12
l Division of General Pediatrics & Adolescent Medicine, Department of Pediatrics , Johns Hopkins University School of Medicine , Baltimore , MD , USA.

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

PMID:
28165855
PMCID:
PMC5873359
[Available on 2019-03-06]
DOI:
10.1080/15592294.2017.1287654

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