title: Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins.
abstract: BACKGROUND
  Asthma is the most common chronic inflammatory disorder in children. The aetiology of asthma pathology is complex and highly heterogeneous, involving the interplay between genetic and environmental risk factors that is hypothesized to involve epigenetic processes. Our aim was to explore whether methylomic variation in early childhood is associated with discordance for asthma symptoms within monozygotic (MZ) twin pairs recruited from the Environmental Risk (E-Risk) longitudinal twin study. We also aimed to identify differences in DNA methylation that are associated with asthma that develops in childhood and persists into early adulthood as these may represent useful prognostic biomarkers.
  
  
  RESULTS
  We examined genome-wide patterns of DNA methylation in buccal cell samples collected from 37 MZ twin pairs discordant for asthma at age 10. DNA methylation at individual CpG sites demonstrated significant variability within discordant MZ twin pairs with the top-ranked nominally significant differentially methylated position (DMP) located in the HGSNAT gene. We stratified our analysis by assessing DNA methylation differences in a sub-group of MZ twin pairs who remained persistently discordant for asthma at age 18. The top-ranked nominally significant DMP associated with persisting asthma is located in the vicinity of the HLX gene, which has been previously implicated in childhood asthma.
  
  
  CONCLUSIONS
  We identified DNA methylation differences associated with childhood asthma in peripheral DNA samples from discordant MZ twin pairs. Our data suggest that differences in DNA methylation associated with childhood asthma which persists into early adulthood are distinct from those associated with asthma which remits.
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Therese M
authors.initials: TM
authors.lastname: Murphy
authors.affiliation: MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Chloe C Y
authors.initials: CC
authors.lastname: Wong
authors.affiliation: MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Arseneault
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Burrage
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Ruby
authors.initials: R
authors.lastname: Macdonald
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Eilis
authors.initials: E
authors.lastname: Hannon
authors.affiliation: MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Fisher
authors.affiliation: MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Antony
authors.initials: A
authors.lastname: Ambler
authors.affiliation: MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK ; Department of Psychology and Neuroscience, Duke University, Durham, NC USA ; Department of Psychiatry and Behavioral Sciences, Duke University Medical School, Durham, NC USA.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Moffitt
authors.affiliation: MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK ; Department of Psychology and Neuroscience, Duke University, Durham, NC USA ; Department of Psychiatry and Behavioral Sciences, Duke University Medical School, Durham, NC USA.
authors.forename: Avshalom
authors.initials: A
authors.lastname: Caspi
authors.affiliation: University of Exeter Medical School, University of Exeter, Exeter, UK ; MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
keywords: Asthma; DNA methylation; Epigenetics; Monozygotic twins