title: Neonatal genome-wide methylation patterns in relation to birth weight in the Norwegian Mother and Child Cohort.
abstract: Although epigenetic regulation plays a critical role in embryonic development, few studies have examined the relationship of epigenome-wide methylation with fetal growth. Using the Infinium HumanMethylation450 BeadChip (Illumina, Inc., San Diego, California) in a substudy of 1,046 infants from the Norwegian Mother and Child Cohort Study (MoBa) enrolled between 1999 and 2008, we examined epigenome-wide cord blood DNA methylation in relation to birth weight. In multivariable-adjusted robust linear regression models, we identified differential methylation at 19 cytosine-guanine dinucleotides (CpGs) associated with either decreased (AT-rich interactive domain 5B (MRF1-like) (ARID5B), 2 CpGs) or increased (x-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), 4 CpGs) birth weight. ARID5B knockout mice have less adipose tissue and significantly lower weight in the postnatal period. XRCC3 plays a key role in the maintenance of chromosome stability and the repair of DNA damage. Although there are fewer data on the other implicated genes, many of these genes have been shown to have roles in developmental processes. This constitutes the largest and most robust study of birth weight using an epigenome-wide methylation platform and offers potential insights into epigenetic mechanisms of fetal growth.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Engel
authors.forename: Bonnie R
authors.initials: BR
authors.lastname: Joubert
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wu
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.forename: Siri E
authors.initials: SE
authors.lastname: Håberg
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Wenche
authors.initials: W
authors.lastname: Nystad
authors.forename: Roy M
authors.initials: RM
authors.lastname: Nilsen
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Shyamal D
authors.initials: SD
authors.lastname: Peddada
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
mesh_terms: D000293:Adolescent; D000328:Adult; D001482:Base Composition / Q000235:genetics; D001724:Birth Weight / Q000235:genetics*; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D009664:Norway; D011247:Pregnancy; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C110901:X-ray repair cross complementing protein 3
keywords: MoBa; Norwegian Mother and Child Cohort Study; birth weight; cord blood; epigenetics; methylation