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

@unpublished{Marzi:2017:10.1101/183541,
author = {Marzi, S and Ribarska, T and Smith, A and Hannon, E and Poschmann, J and Moore, K and Troakes, C and Al-Sarraj, S and Beck, S and Newman, S and Lunnon, K and Schalkwyk, L and Mill, J},
doi = {10.1101/183541},
publisher = {Cold Spring Harbor Laboratory},
title = {A histone acetylome-wide association study of Alzheimer’s disease: neuropathology-associated regulatory variation in the human entorhinal cortex},
url = {http://dx.doi.org/10.1101/183541},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by the progressive accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles in the neocortex. Recent studies have implicated a role for regulatory genomic variation in AD progression, finding widespread evidence for altered DNA methylation associated with neuropathology. To date, however, no study has systematically examined other types of regulatory genomic modifications in AD. In this study, we quantified genome-wide patterns of lysine H3K27 acetylation (H3K27ac) - a robust mark of active enhancers and promoters that is strongly correlated with gene expression and transcription factor binding - in entorhinal cortex samples from AD cases and matched controls (n = 47) using chromatin immunoprecipitation followed by highly parallel sequencing (ChIP-seq). Across ~182,000 robustly detected H3K27ac peak regions, we found widespread acetylomic variation associated with AD neuropathology, identifying 4,162 differential peaks (FDR < 0.05) between AD cases and controls. These differentially acetylated peaks are enriched in disease-specific biological pathways and include regions annotated to multiple genes directly involved in the progression of Aβ and tau pathology (e.g. APP , PSEN1 , PSEN2 , MAPT ), as well as genomic regions containing variants associated with sporadic late-onset AD. This is the first study of variable H3K27ac yet undertaken in AD and the largest study investigating this modification in the entorhinal cortex. In addition to identifying molecular pathways associated with AD neuropathology, we present a framework for genome-wide studies of histone modifications in complex disease, integrating our data with results obtained from genome-wide association studies as well as other epigenetic marks profiled on the same samples.
AU  - Marzi,S
AU  - Ribarska,T
AU  - Smith,A
AU  - Hannon,E
AU  - Poschmann,J
AU  - Moore,K
AU  - Troakes,C
AU  - Al-Sarraj,S
AU  - Beck,S
AU  - Newman,S
AU  - Lunnon,K
AU  - Schalkwyk,L
AU  - Mill,J
DO  - 10.1101/183541
PB  - Cold Spring Harbor Laboratory
PY  - 2017///
TI  - A histone acetylome-wide association study of Alzheimer’s disease: neuropathology-associated regulatory variation in the human entorhinal cortex
UR  - http://dx.doi.org/10.1101/183541
UR  - https://www.biorxiv.org/content/10.1101/183541v1
UR  - http://hdl.handle.net/10044/1/88247
ER  -
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