Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Recessive Inheritance of a Rare Variant in the Nuclear Mitochondrial Gene for AARS2 in Late-Onset Dilated Cardiomyopathy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Randomization of Left-right Asymmetry and Congenital Heart Defects: The Role of DNAH5 in Humans and Mice

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Subsequent Event Risk in Individuals With Established Coronary Heart Disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Genetic stratification of depression in UK Biobank

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genomic medicine as consumer goods

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Dual roles of heparanase in human carotid plaque calcification

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskning

  4. Human Disease Variation in the Light of Population Genomics

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  • Örjan Åkerborg
  • Rapolas Spalinskas
  • Sailendra Pradhananga
  • Anandashankar Anil
  • Pontus Höjer
  • Flore-Anne Poujade
  • Lasse Folkersen
  • Per Eriksson
  • Pelin Sahlén
Vis graf over relationer

BACKGROUND: 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. METHODS: 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. RESULTS: 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 genome-wide association studies variants using haplotype information, thereby identifying additional relevant genes and functions. Importantly, we discovered that a subset of risk variants interact with multiple promoters and their expression levels were strongly correlated. CONCLUSIONS: In summary, we present a catalog of candidate genes regulated by coronary artery disease-related variants and think that it will be an invaluable resource to further the investigation of cardiovascular pathologies and disease.

OriginalsprogEngelsk
TidsskriftCirculation. Genomic and precision medicine
Vol/bind12
Udgave nummer3
Sider (fra-til)e002353
ISSN2574-8300
DOI
StatusUdgivet - mar. 2019

ID: 56747005