| Title: |
The cord blood insulin and mitochondrial DNA content related methylome |
| Authors: |
Reimann, B; Janssen, BG; Alfano, R; Ghantous, A; Espin-Perez, A; De Koko, TM; Saenen, ND; Cox, B; Robinson, O; Chadeau-Hyam, M; Penders, J; Herceg, Z; Vineis, P; Nawrot, TS; Plusquin, M |
| Contributors: |
Medical Research Council (MRC); Commission of the European Communities |
| Publisher Information: |
Frontiers Media |
| Publication Year: |
2019 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Genetics & Heredity; insulin; mitochondrial DNA content; epigenome-wide methylation; cord blood insulin levels; mitochondrial dysfunction; differentially methylated regions; DMRs; ENVIRONAGE; REPULSIVE GUIDANCE MOLECULE; GENE-BODY METHYLATION; POSTTRANSCRIPTIONAL REGULATION; CYTOCHROME-P450 2E1; CELLULAR SENESCENCE; DOPAMINE AGONIST; AIR-POLLUTION; RESISTANCE; EXPOSURE; DISEASE |
| Description: |
Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIRONAGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 × 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p-values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated (r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables (p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A (RGMA) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate alterations in neurodevelopment, histone ... |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
Frontiers in Genetics; http://hdl.handle.net/10044/1/69735; https://dx.doi.org/10.3389/fgene.2019.00325; MR/M501669/1; 308610 |
| DOI: |
10.3389/fgene.2019.00325 |
| Availability: |
http://hdl.handle.net/10044/1/69735; https://doi.org/10.3389/fgene.2019.00325 |
| Rights: |
© 2019 Reimann, Janssen, Alfano, Ghantous, Espín-Pérez, de Kok, Saenen, Cox, Robinson, Chadeau-Hyam, Penders, Herceg, Vineis, Nawrot and Plusquin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Accession Number: |
edsbas.B5D04D95 |
| Database: |
BASE |