Imperial College London
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DrSarahMarzi

Faculty of Medicine, Department of Brain Sciences

Honorary Senior Lecturer
 
 
 
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s.marzi

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Asenius:2020:10.1371/journal.pgen.1009035,
author = {Asenius, F and Gorrie-Stone, TJ and Brew, A and Panchbhaya, Y and Williamson, E and Schalkwyk, LC and Rakyan, VK and Holland, ML and Marzi, SJ and Williams, DJ},
doi = {10.1371/journal.pgen.1009035},
journal = {PLoS Genetics},
pages = {1--28},
title = {The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations},
url = {http://dx.doi.org/10.1371/journal.pgen.1009035},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10−8; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely me
AU  - Asenius,F
AU  - Gorrie-Stone,TJ
AU  - Brew,A
AU  - Panchbhaya,Y
AU  - Williamson,E
AU  - Schalkwyk,LC
AU  - Rakyan,VK
AU  - Holland,ML
AU  - Marzi,SJ
AU  - Williams,DJ
DO  - 10.1371/journal.pgen.1009035
EP  - 28
PY  - 2020///
SN  - 1553-7390
SP  - 1
TI  - The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations
T2  - PLoS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1009035
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000581773200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009035
UR  - http://hdl.handle.net/10044/1/88243
VL  - 16
ER  -
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