Epigenome Wide Association and Stochastic Epigenetic Mutation Analysis on Cord Blood of Preterm Birth

• Published in: International journal of molecular sciences Vol. 21; no. 14; p. 5044
• Main Authors: Spada, Elena, Calzari, Luciano, Corsaro, Luigi, Fazia, Teresa, Mencarelli, Monica, Di Blasio, Anna Maria, Bernardinelli, Luisa, Zangheri, Giulia, Vignali, Michele, Gentilini, Davide
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.07.2020; MDPI
• Subjects: Arrays; Birth; Blood cells; Composition; Cord blood; Deoxyribonucleic acid; DNA; DNA Methylation; DNA Mutational Analysis; Epigenesis, Genetic; Epigenetics; Epigenome; Evaluation; Female; genome-wide; Genome-Wide Association Study; Genomes; Humans; Immune system; Infant; Infant, Newborn; Infinium Human Methylation 450K BeadChip; Levels; Lymphocytes; Male; Mutation; Neonates; Premature birth; Premature Birth - genetics; preterm birth; Statistical analysis; Statistical methods; stochastic epigenetic mutations; Stochastic Processes; Stochasticity; Studies; preterm birth; genome-wide; DNA-methylation; stochastic epigenetic mutations; Infinium Human Methylation 450K BeadChip
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21145044

Preterm birth (PTB) can be defined as the endpoint of a complex process that could be influenced by maternal and environmental factors. Epigenetics recently emerged as an interesting field of investigation since it represents an important mechanism of regulation. This study evaluates epigenetic impact of preterm birth on DNA methylation. Genome-wide DNAm was measured using the Illumina 450K array in cord blood samples obtained from 72 full term and 18 preterm newborns. Lymphocyte composition was calculated based on specific epigenetic markers that are present on the 450k array. Differential methylation analysis was performed both at site and region level; moreover, stochastic epigenetic mutations (SEMs) were also evaluated. The study showed significant differences in blood cell composition between the two groups. Moreover, after multiple testing correction, statistically significant differences in DNA methylation levels emerged between the two groups both at site and region levels. Results obtained were compared to those reported by previous EWAS, leading to a list of more consistent genes associated with PTB. Finally, the SEMs analysis revealed that the burden of SEMs resulted significantly higher in the preterm group. In conclusion, PTB resulted associated to specific epigenetic signatures that involve immune system. Moreover, SEMs analysis revealed an increased epigenetic drift at birth in the preterm group.