Evidence map›Paper›PMID 35735005›Full record

ArticleCirculation2022

Effects of Coronary Artery Disease-Associated Variants on Vascular Smooth Muscle Cells.

Charles U Solomon, David G McVey, Catherine Andreadi, Peng Gong, Lenka Turner, Paulina J Stanczyk, Sonja Khemiri, Julie C Chamberlain, Wei Yang, Tom R Webb and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Effector Genes at the Coronary Artery Disease Risk Locus HarboringJournal of the American Heart Association · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 3 countries.

Charles U Solomon *Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).ORCID 0000-0002-6462-3384
David G McVey *Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).ORCID 0000-0002-6402-2546
Catherine Andreadi *Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).
Peng Gong *Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).
Lenka Turner *Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).
Paulina J Stanczyk *Department of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).
Sonja KhemiriDepartment of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).
Julie C ChamberlainDepartment of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).
Wei YangShantou University Medical College, China (W.Y., S.Y.).
Tom R WebbDepartment of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).ORCID 0000-0001-5998-8226
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).ORCID 0000-0002-3286-8133
Shu YeDepartment of Cardiovascular Sciences, University of Leicester, and National Institute for Health Research Leicester Biomedical Research Centre, UK (C.U.S., D.G.M., C.A., P.G., L.T., P.J.S., S.K., J.C.C., T.R.W., C.P.N., J.N.S., S.Y.).ORCID 0000-0002-4126-4278
NIHR Leicester Biomedical Research Centre · GBNational University of Singapore · SGShantou University · CN

Funding

British Heart Foundation PG/16/9/31995British Heart Foundation PG/18/73/34059British Heart Foundation RG/16/13/32609British Heart Foundation RG/19/9/34655British Heart Foundation SP/16/4/32697British Heart Foundation SP/19/2/344612
6 · The paper itself

Abstract

backgroundGenome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease (CAD). However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. Evidence suggests that the genetic influence on CAD susceptibility may act partly through vascular smooth muscle cells (VSMCs).

methodsWe undertook genotyping, RNA sequencing, and cell behavior assays on a large bank of VSMCs (n>1499). Expression quantitative trait locus and splicing quantitative trait locus analyses were performed to identify genes with an expression that was influenced by CAD-associated variants. To identify candidate causal genes for CAD, we ascertained colocalizations of VSMC expression quantitative trait locus signals with CAD association signals by performing causal variants identification in associated regions analysis and the summary data-based mendelian randomization test. Druggability analysis was then performed on the candidate causal genes. CAD risk variants were tested for associations with VSMC proliferation, migration, and apoptosis. Collective effects of multiple CAD-associated variants on VSMC behavior were estimated by polygenic scores.

resultsApproximately 60% of the known CAD-associated variants showed statistically significant expression quantitative trait locus or splicing quantitative trait locus effects in VSMCs. Colocalization analyses identified 84 genes with expression quantitative trait locus signals that significantly colocalized with CAD association signals, identifying them as candidate causal genes. Druggability analysis indicated that 38 of the candidate causal genes were druggable, and 13 had evidence of drug-gene interactions. Of the CAD-associated variants tested, 139 showed suggestive associations with VSMC proliferation, migration, or apoptosis. A polygenic score model explained up to 5.94% of variation in several VSMC behavior parameters, consistent with polygenic influences on VSMC behavior.

conclusionsThis comprehensive analysis shows that a large percentage of CAD loci can modulate gene expression in VSMCs and influence VSMC behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets.

Indexed as

Coronary Artery DiseaseGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMuscle, Smooth, VascularMyocytes, Smooth MusclePolymorphism, Single NucleotideQuantitative Trait Locicoronary artery diseasegeneticsmuscle, smooth, vasculartranscriptomes

Identifiers

PMID35735005
PMCPMC9484647
OpenAlexW4283394120

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.