title: Sex differences in DNA methylation assessed by 450 K BeadChip in newborns.
abstract: BACKGROUND
  DNA methylation is an important epigenetic mark that can potentially link early life exposures to adverse health outcomes later in life. Host factors like sex and age strongly influence biological variation of DNA methylation, but characterization of these relationships is still limited, particularly in young children.
  
  
  METHODS
  In a sample of 111 Mexican-American subjects (58 girls , 53 boys), we interrogated DNA methylation differences by sex at birth using the 450 K BeadChip in umbilical cord blood specimens, adjusting for cell composition.
  
  
  RESULTS
  We observed that ~3% of CpG sites were differentially methylated between girls and boys at birth (FDR P < 0.05). Of those CpGs, 3031 were located on autosomes, and 82.8% of those were hypermethylated in girls compared to boys. Beyond individual CpGs, we found 3604 sex-associated differentially methylated regions (DMRs) where the majority (75.8%) had higher methylation in girls. Using pathway analysis, we found that sex-associated autosomal CpGs were significantly enriched for gene ontology terms related to nervous system development and behavior. Among hits in our study, 35.9% had been previously reported as sex-associated CpG sites in other published human studies. Further, for replicated hits, the direction of the association with methylation was highly concordant (98.5-100%) with previous studies.
  
  
  CONCLUSIONS
  To our knowledge, this is the first reported epigenome-wide analysis by sex at birth that examined DMRs and adjusted for confounding by cell composition. We confirmed previously reported trends that methylation profiles are sex-specific even in autosomal genes, and also identified novel sex-associated CpGs in our methylome-wide analysis immediately after birth, a critical yet relatively unstudied developmental window.
authors.affiliation: School of Public Health, University of California, 733 University Hall, School of Public Health, UC, Berkeley, CA, 94720-7360, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Yousefi
authors.affiliation: School of Public Health, University of California, 733 University Hall, School of Public Health, UC, Berkeley, CA, 94720-7360, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Huen
authors.affiliation: School of Public Health, University of California, 733 University Hall, School of Public Health, UC, Berkeley, CA, 94720-7360, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Davé
authors.affiliation: School of Public Health, University of California, 733 University Hall, School of Public Health, UC, Berkeley, CA, 94720-7360, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Barcellos
authors.affiliation: School of Public Health, University of California, 733 University Hall, School of Public Health, UC, Berkeley, CA, 94720-7360, USA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
authors.affiliation: School of Public Health, University of California, 733 University Hall, School of Public Health, UC, Berkeley, CA, 94720-7360, USA. ninah@berkeley.edu.
authors.forename: Nina
authors.initials: N
authors.lastname: Holland
mesh_terms: D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D057890:Epigenomics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008297:Male