title: PGC1α promoter methylation in blood at 5-7 years predicts adiposity from 9 to 14 years (EarlyBird 50).
abstract: The early environment, acting via epigenetic processes, is associated with differential risk of cardiometabolic disease (CMD), which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analyzed DNA methylation in the peroxisome proliferator-activated receptor γ coactivator 1α promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years of age by pyrosequencing. Body composition was measured annually by dual X-ray absorptiometry, physical activity by accelerometry, and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven cytosine guanine dinucleotide (CpG) loci were identified that showed no significant temporal change or association with leukocyte populations. Modeling using generalized estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing, and activity. Methylation of one predictive locus modified binding of the proadipogenic pre-B-cell leukemia homeobox-1/homeobox 9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk.
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, U.K.National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, U.K.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Clarke-Harris
authors.affiliation: University of Exeter Medical School, Exeter, U.K.
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Wilkin
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, U.K.
authors.forename: Joanne
authors.initials: J
authors.lastname: Hosking
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, U.K.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pinkney
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, U.K.
authors.forename: Alison N
authors.initials: AN
authors.lastname: Jeffery
authors.affiliation: University of Exeter Medical School, Exeter, U.K.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Metcalf
authors.affiliation: National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton, and University Hospital Southampton National Health Service Foundation Trust, Southampton, U.K.Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, U.K.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Godfrey
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, U.K.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Voss
authors.affiliation: Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, U.K. k.a.lillycrop@soton.ac.uk.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Lillycrop
authors.affiliation: Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, U.K.
authors.forename: Graham C
authors.initials: GC
authors.lastname: Burdge
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000367:Age Factors; D001773:Blood Cells / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000175:diagnosis* / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011379:Prognosis; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors