title: DNA methylation provides insight into intergenerational risk for preterm birth in African Americans.
abstract: African Americans are at increased risk for spontaneous preterm birth (PTB). Though PTB is heritable, genetic studies have not identified variants that account for its intergenerational risk, prompting the hypothesis that epigenetic factors may also contribute. The objective of this study was to evaluate DNA methylation from maternal leukocytes to identify patterns specific to PTB and its intergenerational risk. DNA from peripheral leukocytes from African American women that delivered preterm (24-34 weeks; N = 16) or at term (39-41 weeks; N = 24) was assessed for DNA methylation using the HumanMethylation450 BeadChip. In maternal samples, 17,829 CpG sites associated with PTB, but no CpG site remained associated after correction for multiple comparisons. Examination of paired maternal-fetal samples identified 5,171 CpG sites in which methylation of maternal samples correlated with methylation of her respective fetus (FDR < 0.05). These correlated sites were enriched for association with PTB in maternal leukocytes. The majority of correlated CpG sites could be attributed to one or more genetic variants. They were also significantly more likely to be in genes involved in metabolic, cardiovascular, and immune pathways, suggesting a role for genetic and environmental contributions to PTB risk and chronic disease. The results of this study may provide insight into the factors underlying intergenerational risk for PTB and its consequences.
authors.affiliation: a Genetics and Molecular Biology Program; Emory University ; Atlanta , GA USA.
authors.forename: Sasha E
authors.initials: SE
authors.lastname: Parets
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
authors.forename: Varun
authors.initials: V
authors.lastname: Kilaru
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Smith
mesh_terms: D000328:Adult; D001741:Black or African American / Q000208:ethnology / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
keywords: African American; DNA methylation; DOHaD; EWAS; epigenetic; gestational age; heritability; preterm birth