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

Golareh Agha, Hanine Hajj, Sheryl L. Rifas-Shiman, Allan C. Just, Marie-France Hivert, Heather H. Burris, Xihong Lin, Augusto A. Litonjua, Emily Oken, Dawn L. DeMeo, Matthew W. Gillman, Andrea A. Baccarelli
2016 Clinical Epigenetics  
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.
more » ... s: 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.
doi:10.1186/s13148-016-0285-3 pmid:27891191 pmcid:PMC5112715 fatcat:5n5f5iwfkbdwtf3ipgc47ssbme