Cell-type-specific insight into function of risk factors in coronary
artery disease

Date:
July 8, 2021
Source:
University of Eastern Finland
Summary:
Using single cell technology, a new study sheds light on the
significance of genetic risk factors for, and the diversity of
cells involved in, the development of coronary artery disease. The
researchers analysed human atherosclerotic lesions to map the
chromatin accessibility of more than 7,000 cells.



FULL STORY ========================================================================== Using single cell technology, a new study sheds light on the significance
of genetic risk factors for, and the diversity of cells involved in,
the development of coronary artery disease. The researchers analysed
human atherosclerotic lesions to map the chromatin accessibility of
more than 7,000 cells. The chromatin accessibility is known to reflect
active regions and genes in the genome. The findings were published in Circulation Research.


========================================================================== Genome-wide association studies of the human genome have identified over
200 loci associated with coronary artery disease. More than 90% of them
are located outside protein-coding genes, in so called cis-regulatory
elements, whose significance in the pathogenesis of coronary artery
disease remains unclear.

Previous research has demonstrated that the development of coronary artery disease involves a variety of different cells and their subtypes. The
now- published study is the first to use single cell technology to map epigenetic changes in these cells. The researchers used the ATAC-seq
sequencing method to discover the nuclear chromatin structure of
endothelial cells and smooth muscle cells, as well as immune system
monocytes, macrophages, NK/T and B cells, providing a unique resource
to study the cell-type specific activity of the cis-regulatory elements
in the disease affected vessel wall.

The study demonstrated that genetic risk variants associated with coronary artery disease are particularly enriched in cis-regulatory elements
specific to endothelial and smooth muscle cells, indicating that these
cells play a significant role in transmitting susceptibility to the
disease. Based on chromatin accessibility mapping and gene expression
data, the researchers were able to identify putative target genes for approximately 30% of all known loci associated with coronary artery
disease. In addition, the researchers performed genome-wide experimental fine-mapping of the variants, allowing them to identify potential causal single-nucleotide polymorphisms and the associated target gene for over
30 loci that have been linked to coronary artery disease.

The study also presented a number of examples of how the chromatin accessibility and gene expression data can be used to predict target
cells via which the function of the genetic changes associated with
the disease is transmitted in the tissue. This is a significant step
forward that helps to understand the real functional significance of
risk variants in the pathophysiology of coronary artery disease. In
the future, this information can be used to develop more effective,
safer and more individualised treatments for coronary artery disease.

========================================================================== Story Source: Materials provided by University_of_Eastern_Finland. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Tiit O"rd, Kadri O~unap, Lindsey Stolze, Re'douane Aherrahrou,
Valtteri
Nurminen, Ilakya Selvarajan, Anu Toropainen, Tapio Lo"nnberg, Einari
Aavik, Seppo Yla-Herttuala, Mete Civelek, Casey E Romanoski, Minna
U Kaikkonen. Single-Cell Epigenomics and Functional Fine-Mapping
of Atherosclerosis GWAS Loci. Circulation Research, 2021; DOI:
10.1161/ CIRCRESAHA.121.318971 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210708083910.htm

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