Imperial College London
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DrSarahMarzi

Faculty of Medicine, Department of Brain Sciences

Honorary Senior Lecturer
 
 
 
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Contact

 

s.marzi

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hannon:2019:10.1186/s13041-019-0429-4,
author = {Hannon, E and Marzi, SJ and Schalkwyk, LS and Mill, J},
doi = {10.1186/s13041-019-0429-4},
journal = {Molecular Brain},
title = {Genetic risk variants for brain disorders are enriched in cortical H3K27ac domains},
url = {http://dx.doi.org/10.1186/s13041-019-0429-4},
volume = {12},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Most variants associated with complex phenotypes in genome-wide association studies (GWAS) do not directly index coding changes affecting protein structure. Instead they are hypothesized to influence gene regulation, with common variants associated with disease being enriched in regulatory domains including enhancers and regions of open chromatin. There is interest, therefore, in using epigenomic annotation data to identify the specific regulatory mechanisms involved and prioritize risk variants. We quantified lysine H3K27 acetylation (H3K27ac) - a robust mark of active enhancers and promoters that is strongly correlated with gene expression and transcription factor binding – across the genome in entorhinal cortex samples using chromatin immunoprecipitation followed by highly parallel sequencing (ChIP-seq). H3K27ac peaks were called using high quality reads combined across all samples and formed the basis of partitioned heritability analysis using LD score regression along with publicly-available GWAS results for seven psychiatric and neurodegenerative traits. Heritability for all seven brain traits was significantly enriched in these H3K27ac peaks (enrichment ranging from 1.09–2.13) compared to regions of the genome containing other active regulatory and functional elements across multiple cell types and tissues. The strongest enrichments were for amyotrophic lateral sclerosis (ALS) (enrichment = 2.19; 95% CI = 2.12–2.27), autism (enrichment = 2.11; 95% CI = 2.05–2.16) and major depressive disorder (enrichment = 2.04; 95% CI = 1.92–2.16). Much lower enrichments were observed for 14 non-brain disorders, although we identified enrichment in cortical H3K27ac domains for body mass index (enrichment = 1.16; 95% CI = 1.13–1.19), ever smoked (enrichment = 2.07; 95% CI = 2.04–2.10), HDL (enrich
AU  - Hannon,E
AU  - Marzi,SJ
AU  - Schalkwyk,LS
AU  - Mill,J
DO  - 10.1186/s13041-019-0429-4
PY  - 2019///
SN  - 1756-6606
TI  - Genetic risk variants for brain disorders are enriched in cortical H3K27ac domains
T2  - Molecular Brain
UR  - http://dx.doi.org/10.1186/s13041-019-0429-4
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000459816900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-019-0429-4
UR  - http://hdl.handle.net/10044/1/77073
VL  - 12
ER  -
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