Imperial College London

DrOliverRobinson

Faculty of MedicineSchool of Public Health

Lecturer in Molecular Epidemiology
 
 
 
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Contact

 

o.robinson

 
 
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Location

 

1103Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Reimann:2019:10.3389/fgene.2019.00325,
author = {Reimann, B and Janssen, BG and Alfano, R and Ghantous, A and Espin-Perez, A and de, Koko TM and Saenen, ND and Cox, B and Robinson, O and Chadeau-Hyam, M and Penders, J and Herceg, Z and Vineis, P and Nawrot, TS and Plusquin, M},
doi = {10.3389/fgene.2019.00325},
journal = {Frontiers in Genetics},
title = {The cord blood insulin and mitochondrial DNA content related methylome},
url = {http://dx.doi.org/10.3389/fgene.2019.00325},
volume = {10},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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
AU - Reimann,B
AU - Janssen,BG
AU - Alfano,R
AU - Ghantous,A
AU - Espin-Perez,A
AU - de,Koko TM
AU - Saenen,ND
AU - Cox,B
AU - Robinson,O
AU - Chadeau-Hyam,M
AU - Penders,J
AU - Herceg,Z
AU - Vineis,P
AU - Nawrot,TS
AU - Plusquin,M
DO - 10.3389/fgene.2019.00325
PY - 2019///
SN - 1664-8021
TI - The cord blood insulin and mitochondrial DNA content related methylome
T2 - Frontiers in Genetics
UR - http://dx.doi.org/10.3389/fgene.2019.00325
UR - http://hdl.handle.net/10044/1/69735
VL - 10
ER -