Birth weight-for-gestational age is associated with DNA methylation at birth and in childhood.
Clin Epigenetics
; 8: 118, 2016.
Article
em En
| MEDLINE
| ID: mdl-27891191
ABSTRACT
BACKGROUND:
Both higher and lower fetal growth are associated with cardio-metabolic health later in life, suggesting that prenatal developmental programming determines long-term cardiovascular disease risk. Epigenetic mechanisms, which orchestrate fetal growth and development, may offer insight on the early programming of health and disease. We investigated whether birth weight-for-gestational is associated with DNA methylation at birth and mid-childhood, measured via the Infinium 450K array. METHODS/RESULTS:
Participants were from Project Viva, a pre-birth cohort of pregnant women and their children in Eastern Massachusetts. After exclusion of participants with maternal type 1 or 2 diabetes and gestational age <34 weeks, we used DNA methylation assays from 476 venous umbilical cord blood samples and a subset of 235 who additionally had peripheral blood samples available in mid-childhood (age 7-10 years). Among 392,918 CpG sites analyzed, birth weight-for-gestational age z-score was associated with cord blood DNA methylation at 34 CpGs (false discovery rate P < 0.05), after adjusting for maternal age, race/ethnicity, education, smoking, parity, delivery mode, pre-pregnancy BMI, gestational diabetes status, child sex, and estimated cord blood cell proportions based on a cord blood reference panel. Two of these CpGs were previously reported in epigenome-wide analyses of birth weight, and several other CpGs map to genes relevant to fetal growth and development. Namely, higher birth weight-for-gestational age was associated with higher methylation at four CpGs at the PBX1 locus (e.g., ß (95% CI) for lead signal at cg06750897 = 1.9 (1.2, 2.6)), which encodes a transcription factor that regulates embryonic development. Birth weight-for-gestational age was also associated with mid-childhood blood DNA methylation at four of the 34 CpGs identified in cord blood analyses, including sites at the PBX1 locus described.CONCLUSIONS:
We identified CpG sites where birth weight-for-gestational age was associated with DNA methylation at birth, and for a subset of these sites, birth weight-for-gestational age was also associated with DNA methylation at mid-childhood.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peso ao Nascer
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Proteínas Proto-Oncogênicas
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Metilação de DNA
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Proteínas de Ligação a DNA
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Child
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Female
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Humans
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Pregnancy
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article