title: Birth weight-for-gestational age is associated with DNA methylation at birth and in childhood.
abstract: 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.
  
  
  
  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 agez-score was associated with cord blood DNA methylation at 34 CpGs (false discovery rateP< 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 thePBX1locus (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 thePBX1locus described.
  
  
  
  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.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY 10032 USA.
authors.forename: Golareh
authors.identifier: 0000-0002-4719-061X
authors.initials: G
authors.lastname: Agha
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Boston, MA USA.
authors.forename: Hanine
authors.initials: H
authors.lastname: Hajj
authors.affiliation: Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA USA.
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Rifas-Shiman
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors.forename: Allan C
authors.initials: AC
authors.lastname: Just
authors.affiliation: Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA USA.|Diabetes Unit, Massachusetts General Hospital, Boston, MA USA.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hivert
authors.affiliation: Department of Neonatology, Beth Israel Deaconess Medical Center, Department of Pediatrics, Harvard Medical School, Boston, MA USA.|Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Burris
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA USA.
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Boston, MA USA.
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.affiliation: Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Oken
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA USA.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: DeMeo
authors.affiliation: Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA USA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Gillman
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY 10032 USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D001724:Birth Weight / Q000235:genetics*; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood; D047109:Fetal Development; D005865:Gestational Age; D006801:Humans; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C083400:PBX1 protein, human
keywords: Birth weight; DNA methylation; Epigenetics