title: Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function.
abstract: DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early-life stress and neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm, and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth<33 weeks gestation) and healthy controls (birth>37 weeks), and a genome-wide analysis of DNAm was performed; diffusion magnetic resonance imaging (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components (PC) analysis was used to investigate the contribution of MRI features and clinical variables to variance in DNAm. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants compared with controls; 10 of these have neural functions. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 PCs; corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sparrow
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Manning
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: J
authors.initials: J
authors.lastname: Cartier
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: D
authors.initials: D
authors.lastname: Anblagan
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Bastin
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Piyasena
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: R
authors.initials: R
authors.lastname: Pataky
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Moore
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: S I
authors.initials: SI
authors.lastname: Semple
authors.affiliation: Department of Radiology, NHS Lothian, Edinburgh, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Wilkinson
authors.affiliation: Department of Pathology, NHS Lothian, Edinburgh, UK.
authors.forename: M
authors.initials: M
authors.lastname: Evans
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Drake
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.|Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Boardman
mesh_terms: D001921:Brain / Q000503:physiopathology*; D019175:DNA Methylation / Q000502:physiology*; D038524:Diffusion Magnetic Resonance Imaging; D057890:Epigenomics / Q000379:methods*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D008297:Male; D025341:Principal Component Analysis