Birth weight-for-gestational age is associated with DNA methylation at birth and in childhood

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Birth weight-for-gestational age is associated with DNA methylation at birth and in childhood

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Title: Birth weight-for-gestational age is associated with DNA methylation at birth and in childhood
Author: Agha, Golareh; Hajj, Hanine; Rifas-Shiman, Sheryl L.; Just, Allan C.; Hivert, Marie-France; Burris, Heather H.; Lin, Xihong; Litonjua, Augusto A.; Oken, Emily; DeMeo, Dawn L.; Gillman, Matthew W.; Baccarelli, Andrea A.

Note: Order does not necessarily reflect citation order of authors.

Citation: Agha, G., H. Hajj, S. L. Rifas-Shiman, A. C. Just, M. Hivert, H. H. Burris, X. Lin, et al. 2016. “Birth weight-for-gestational age is associated with DNA methylation at birth and in childhood.” Clinical Epigenetics 8 (1): 118. doi:10.1186/s13148-016-0285-3. http://dx.doi.org/10.1186/s13148-016-0285-3.
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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., β (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. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0285-3) contains supplementary material, which is available to authorized users.
Published Version: doi:10.1186/s13148-016-0285-3
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112715/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626177
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