DNA methylation in relation to gestational age and brain dysmaturation in preterm infants

• Published in: Brain communications 2022, Vol.4 (2), p.fcac056
• Main Authors: Wheater, Emily N. W., Galdi, Paola, McCartney, Daniel L., Blesa, Manuel, Sullivan, Gemma, Stoye, David Q., Lamb, Gillian, Sparrow, Sarah, Murphy, Lee, Wrobel, Nicola, Quigley, Alan J., Semple, Scott, Thrippleton, Michael J., Wardlaw, Joanna M., Bastin, Mark E., Marioni, Riccardo E., Cox, Simon R., Boardman, James P.
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2632-1297; 2632-1297
• DOI: 10.1093/braincomms/fcac056

Abstract Preterm birth is associated with dysconnectivity of structural brain networks and is a leading cause of neurocognitive impairment in childhood. Variation in DNA methylation is associated with early exposure to extrauterine life but there has been little research exploring its relationship with brain development. Using genome-wide DNA methylation data from the saliva of 258 neonates, we investigated the impact of gestational age on the methylome and performed functional analysis to identify enriched gene sets from probes that contributed to differentially methylated probes or regions. We tested the hypothesis that variation in DNA methylation could underpin the association between low gestational age at birth and atypical brain development by linking differentially methylated probes with measures of white matter connectivity derived from diffusion MRI metrics: peak width skeletonized mean diffusivity, peak width skeletonized fractional anisotropy and peak width skeletonized neurite density index. Gestational age at birth was associated with widespread differential methylation at term equivalent age, with genome-wide significant associations observed for 8870 CpG probes (P