title: Longitudinal analysis of DNA methylation associated with birth weight and gestational age.
abstract: Gestational age (GA) and birth weight have been implicated in the determination of long-term health. It has been hypothesized that changes in DNA methylation may mediate these long-term effects. We obtained DNA methylation profiles from cord blood and peripheral blood at ages 7 and 17 in the same children from the Avon Longitudinal Study of Parents and Children. Repeated-measures data were used to investigate changes in birth-related methylation during childhood and adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify possible mediation of health effects by DNA methylation. In cord blood, methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites with birth weight. Methylation changed in the majority of these sites over time, but neither birth characteristic was strongly associated with methylation at age 7 or 17 (using a conservative correction for multiple testing of P < 1.03 × 10(-7)), suggesting resolution of differential methylation by early childhood. Associations were observed between birth weight-associated CpG sites and phenotypic characteristics in childhood. One strong association involved birth weight, methylation of a CpG site proximal to the NFIX locus and bone mineral density at age 17. Analysis of serial methylation from birth to adolescence provided evidence for a lack of persistence of methylation differences beyond early childhood. Sites associated with birth weight were linked to developmental genes and have methylation levels which are associated with developmental phenotypes. Replication and interrogation of causal relationships are needed to substantiate whether methylation differences at birth influence the association between birth weight and development.
authors: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, andrew.simpkin@bristol.ac.uk.
authors: Andrew J
authors: AJ
authors: Simpkin
authors: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol.
authors: Matthew
authors: M
authors: Suderman
authors: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol.
authors: Tom R
authors: TR
authors: Gaunt
authors: School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors: Oliver
authors: O
authors: Lyttleton
authors: School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK and.
authors: Wendy L
authors: WL
authors: McArdle
authors: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol.
authors: Susan M
authors: SM
authors: Ring
authors: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol.
authors: Kate
authors: K
authors: Tilling
authors: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol.
authors: George
authors: G
authors: Davey Smith
authors: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors: Caroline L
authors: CL
authors: Relton
mesh_terms: D000293:Adolescent; D001724:Birth Weight; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051839:NFI Transcription Factors; C000594474:NFIX protein, human