Imperial College London

DrAbbasDehghan

Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

157Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Walton:2018:10.1101/397836,
author = {Walton, E and Hemani, G and Dehghan, A and Relton, C and Smith, GD},
doi = {10.1101/397836},
publisher = {Cold Spring Harbor Laboratory},
title = {Systematic evaluation of the causal relationship between DNA methylation and C-reactive protein},
url = {http://dx.doi.org/10.1101/397836},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - UNPB
AB - <jats:title>Abstract</jats:title><jats:p>Elevated C-reactive protein (CRP) levels are an indicator of chronic low-grade inflammation. Epigenetic modifications, including DNA methylation, have been linked to CRP, but systematic investigations into potential underlying causal relationships have not yet been performed.</jats:p><jats:p>We systematically performed two-sample Mendelian randomization and colocalization analysis between CRP and DNA methylation levels, using GWAS and EWAS summary statistics as well as individual level data available through the ARIES subset of the Avon Longitudinal Study of Parents and Children (ALSPAC; 1,616 participants).</jats:p><jats:p>We found no convincing examples for a causal association from CRP to DNA methylation. Testing for the reverse (a putative causal effect of DNA methylation on CRP), we found three CpG sites that had shared genetic effects with CRP levels after correcting for multiple testing (cg26470501 (offspring: beta=0.07 [0.03, 0.11]; mothers: beta=0.08 [0.04, 0.13]), cg27023597 (offspring: beta=0.18 [0.10, 0.25]; mothers: beta=0.20 [0.12, 0.28]) and cg12054453 (offspring: beta=0.09 [0.05, 0.13])) influenced CRP levels. For all three CpG sites, linked to the genes <jats:italic>TMEM49, BCL3</jats:italic> and <jats:italic>MIR21</jats:italic>, increased methylation related to an increase in CRP levels. Two CpGs (cg27023597 and cg12054453) were influenced by SNPs in genomic regions that had not previously been implicated in CRP GWASs, implicating them as novel genetic associations.</jats:p><jats:p>Overall, our findings suggest that CRP associations with DNA methylation are more likely to be driven by either confounding or causal influences of DNA methylation on CRP levels, rather than the reverse.</jats:p>
AU - Walton,E
AU - Hemani,G
AU - Dehghan,A
AU - Relton,C
AU - Smith,GD
DO - 10.1101/397836
PB - Cold Spring Harbor Laboratory
PY - 2018///
TI - Systematic evaluation of the causal relationship between DNA methylation and C-reactive protein
UR - http://dx.doi.org/10.1101/397836
ER -