title: CpG Methylation across the adipogenic PPARγ gene and its relationship with birthweight and child BMI at 9 years.
abstract: BACKGROUND
  To examine methylation of the peroxisome proliferator-activated receptor γ (PPARγ) gene and its relationship with child weight status, at birth and 9 years.
  
  
  METHODS
  We measured PPARγ methylation across 23 CpG sites using the Infinium Illumina 450 k array for children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort at birth (N = 373) and 9 years (N = 245).
  
  
  RESULTS
  Methylation level correlation patterns across the 23 PPARγ CpG sites were conserved between birth and 9-year ages. We found high inter-CpG correlations between sites 1-3 (methylation block 1) and also between sites 18-23 (methylation block 2) for both time points, although these patterns were less pronounced at 9 years. Additionally, sites 1-3 (north shore) had the highest intra-CpG correlations over time (r = 0.24, 0.42, and 0.3; P = 0.002, P < 0.001, P < 0.001, respectively). PPARγ methylation levels tended to increase with age, and the largest differences were observed for north shore sites (7.4%). Adjusting for sex, both site 1 and site 20 (gene body) methylation at birth was significantly and inversely associated with birth weight (β = -0.13, P = 0.033; β = -0.09, P = 0.025, respectively). Similarly, we found that site 1 and site 20 methylation at 9 years was significantly and inversely associated with 9-year BMI z-score (β = -0.41, P = 0.015; β = -0.23, P = 0.045, respectively).
  
  
  CONCLUSIONS
  Our results indicate that PPARγ methylation is highly organized and conserved over time, and highlight the potential functional importance of north shore sites, adding to a better understanding of regional human methylome patterns. Overall, our results suggest that PPARγ methylation may be associated with child body size.
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, 733 University Hall, Berkeley, CA, 94720-7360, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Volberg
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, 733 University Hall, Berkeley, CA, 94720-7360, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Yousefi
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, 733 University Hall, Berkeley, CA, 94720-7360, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Huen
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, 733 University Hall, Berkeley, CA, 94720-7360, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Harley
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, 733 University Hall, Berkeley, CA, 94720-7360, USA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
authors.affiliation: Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, 733 University Hall, Berkeley, CA, 94720-7360, USA. ninah@berkeley.edu.
authors.forename: Nina
authors.initials: N
authors.lastname: Holland
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D047495:PPAR gamma / Q000235:genetics*
chemical_list: D047495:PPAR gamma
keywords: Birth cohort study; Children; DNA methylation; Epigenetics; Newborns; Obesity; PPARγ; Whole blood