High-Resolution Regulatory Maps Connect Vascular Risk Variants to Disease-Related Pathways.

Circulation. Genomic and Precision Medicine
Örjan ÅkerborgPelin Sahlén

Abstract

Genetic variant landscape of coronary artery disease is dominated by noncoding variants among which many occur within putative enhancers regulating the expression levels of relevant genes. It is crucial to assign the genetic variants to their correct genes both to gain insights into perturbed functions and better assess the risk of disease. In this study, we generated high-resolution genomic interaction maps (≈750 bases) in aortic endothelial, smooth muscle cells and THP-1 (human leukemia monocytic cell line) macrophages stimulated with lipopolysaccharide using Hi-C coupled with sequence capture targeting 25 429 features, including variants associated with coronary artery disease. We also sequenced their transcriptomes and mapped putative enhancers using chromatin immunoprecipitation with an antibody against H3K27Ac. The regions interacting with promoters showed strong enrichment for enhancer elements and validated several previously known interactions and enhancers. We detected interactions for 727 risk variants obtained by genome-wide association studies and identified novel, as well as established genes and functions associated with cardiovascular diseases. We were able to assign potential target genes for additional 398 gen...Continue Reading

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Citations

Jun 5, 2020·Circulation Research·Christoph D RauYibin Wang
Mar 9, 2021·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Xi PengDimitrios Avramopoulos
Oct 19, 2020·The Journal of Allergy and Clinical Immunology·Pelin SahlénIsabel Tapia-Páez
May 1, 2021·Genome Biology and Evolution·Pelin SahlénPeter Savolainen

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Software Mentioned

CARDIoGRAMplusC4D
topGO
Gene Enrichment Analysis Using
HiCap
ChipAtlas
Genomic Regions Enrichment of Annotations Tool package Gene En...
Dist
Genomic Regions Enrichment of Annotations Tool
Prom
Gviz

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