Epigenetics of complex traits and diseases
Thousands of genetic and epigenetic variants have been identified for many common diseases including cancer through genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS). To advance the complex interpretation of both GWAS and EWAS results, I developed new software tool...
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ndltd-bl.uk-oai-ethos.bl.uk-7470762019-03-05T15:54:01ZEpigenetics of complex traits and diseasesBreeze, Charles E.2017Thousands of genetic and epigenetic variants have been identified for many common diseases including cancer through genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS). To advance the complex interpretation of both GWAS and EWAS results, I developed new software tools (FORGE2 and eFORGE) for the analysis and interpretation of GWAS and EWAS data, respectively. Both tools determine the cell type-specific regulatory component of a set of target regions (either GWAS-identified genetic variants or EWAS-identified differentially methylated positions). This is achieved by detecting enrichment of overlap with histone mark peaks or DNase I hypersensitive sites across hundreds of tissues, primary cell types, and cell lines from the ENCODE, Roadmap Epigenomics, and BLUEPRINT projects. Application of both tools to publicly available datasets identified novel disease-relevant cell types for many common diseases, a stem cell-like signature in cancer EWAS, and also demonstrated the ability to detect cell-composition effects for EWAS performed on heterogeneous tissues. To complement these bioinformatics efforts and validate selected variants predicted by FORGE2, eFORGE and additional analyses, I performed conformation capture using 4C-seq to fine-map the 3D context of the genomic regions involved, uncovering novel interactions for autoimmunity-associated variants and IKZF3.616.99University College London (University of London)https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747076http://discovery.ucl.ac.uk/10038878/Electronic Thesis or Dissertation |
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616.99 Breeze, Charles E. Epigenetics of complex traits and diseases |
description |
Thousands of genetic and epigenetic variants have been identified for many common diseases including cancer through genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS). To advance the complex interpretation of both GWAS and EWAS results, I developed new software tools (FORGE2 and eFORGE) for the analysis and interpretation of GWAS and EWAS data, respectively. Both tools determine the cell type-specific regulatory component of a set of target regions (either GWAS-identified genetic variants or EWAS-identified differentially methylated positions). This is achieved by detecting enrichment of overlap with histone mark peaks or DNase I hypersensitive sites across hundreds of tissues, primary cell types, and cell lines from the ENCODE, Roadmap Epigenomics, and BLUEPRINT projects. Application of both tools to publicly available datasets identified novel disease-relevant cell types for many common diseases, a stem cell-like signature in cancer EWAS, and also demonstrated the ability to detect cell-composition effects for EWAS performed on heterogeneous tissues. To complement these bioinformatics efforts and validate selected variants predicted by FORGE2, eFORGE and additional analyses, I performed conformation capture using 4C-seq to fine-map the 3D context of the genomic regions involved, uncovering novel interactions for autoimmunity-associated variants and IKZF3. |
author |
Breeze, Charles E. |
author_facet |
Breeze, Charles E. |
author_sort |
Breeze, Charles E. |
title |
Epigenetics of complex traits and diseases |
title_short |
Epigenetics of complex traits and diseases |
title_full |
Epigenetics of complex traits and diseases |
title_fullStr |
Epigenetics of complex traits and diseases |
title_full_unstemmed |
Epigenetics of complex traits and diseases |
title_sort |
epigenetics of complex traits and diseases |
publisher |
University College London (University of London) |
publishDate |
2017 |
url |
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747076 |
work_keys_str_mv |
AT breezecharlese epigeneticsofcomplextraitsanddiseases |
_version_ |
1718998614891560960 |