Evidence map›Paper›PMID 39606421›Full record

ArticlemedRxiv : the preprint server for health sciences2024

Single cell variant to enhancer to gene map for coronary artery disease.

Junedh M Amrute, Paul C Lee, Ittai Eres, Chang Jie Mick Lee, Andrea Bredemeyer, Maya U Sheth, Tracy Yamawaki, Rijan Gurung, Chukwuemeka Anene-Nzelu, Wei-Lin Qiu and 24 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors.

Junedh M AmruteCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.ORCID 0000-0002-6851-0168
Paul C LeeCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Ittai EresAmgen Research, South San Francisco, CA, 94080, USA.
Chang Jie Mick LeeCardiovascular Metabolic Disease Translational Research Programme, National University Health System, Centre for Translational Medicine, 14 Medical Drive, Singapore 117599, Singapore.
Andrea BredemeyerCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Maya U ShethDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Tracy YamawakiAmgen Research, South San Francisco, CA, 94080, USA.
Rijan GurungCardiovascular Metabolic Disease Translational Research Programme, National University Health System, Centre for Translational Medicine, 14 Medical Drive, Singapore 117599, Singapore.
Chukwuemeka Anene-NzeluMontreal Heart Institute, Montreal, 5000 Rue Belanger, QC, H1T 1C8, Canada.
Wei-Lin QiuDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.
Soumya KunduDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Daniel Y LiDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94305.
Markus RamsteDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94305.
Daniel LuAmgen Research, South San Francisco, CA, 94080, USA.
Anthony TanDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Chul-Joo KangCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Ryan E WagonerCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Arturo AlisioCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Paul ChengDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94305.ORCID 0000-0003-3429-2702
Quanyi ZhaoDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94305.
Clint L MillerCenter for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville.
Ira M HallCenter for Genomic Health, Yale University, New Haven, CT, 06510, USA.ORCID 0000-0003-4442-6655
Rajat M GuptaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Yi-Hsiang HsuAmgen Research, South San Francisco, CA, 94080, USA.
Saptarsi M HaldarAmgen Research, South San Francisco, CA, 94080, USA.
Kory J LavineCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Simon JacksonAmgen Research, South San Francisco, CA, 94080, USA.
Robin AnderssonDepartment of Biology, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0003-1516-879X
Jesse M EngreitzDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Roger S-Y FooCardiovascular Metabolic Disease Translational Research Programme, National University Health System, Centre for Translational Medicine, 14 Medical Drive, Singapore 117599, Singapore.
Chi-Ming LiAmgen Research, South San Francisco, CA, 94080, USA.
Brandon AsonAmgen Research, South San Francisco, CA, 94080, USA.
Thomas QuertermousDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, CA 94305.ORCID 0000-0002-7645-9067
Nathan O StitzielCenter for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA.ORCID 0000-0002-4963-8211

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Supplement Proposal: Accelerated Genome Aggregation and Joint Variant Calling EffortUM1HG008853 · NHGRI · WASHINGTON UNIVERSITY · PI HALL, IRA M, MILBRANDT, JEFFREY D · 2016 to 2020
$76.2M
Stanford Mendelian Genomics Research CenterU01HG011762 · NHGRI · STANFORD UNIVERSITY · PI Jonathan Adam Bernstein, Stephen Montgomery · 2021 to 2026
$16.7M
Stanford Center for Connecting DNA Variants to Function and PhenotypeUM1HG011972 · NHGRI · STANFORD UNIVERSITY · PI JESSE M ENGREITZ, THOMAS QUERTERMOUS · 2021 to 2026
$10.5M
Causal variant association mechanisms in TCF21 binding coronary disease lociR01HL134817 · NHLBI · STANFORD UNIVERSITY · PI THOMAS QUERTERMOUS · 2017 to 2026
$6.2M
The SMAD3 signaling network in coronary artery disease riskR01HL139478 · NHLBI · STANFORD UNIVERSITY · PI THOMAS QUERTERMOUS · 2018 to 2026
$3.7M
Mapping, modeling, and manipulating 3D contacts in vascular cells to connect risk variants to disease genesR01HL159176 · NHLBI · STANFORD UNIVERSITY · PI ENGREITZ, JESSE M · 2022 to 2025
$2.8M
PDGFD regulates a transcriptional network to modulate smooth muscle cell transition and coronary artery disease riskR01HL156846 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2021 to 2024
$2.7M
High-throughput cellular genetics to connect noncoding variants to coronary artery disease genesR01HL164811 · NHLBI · BROAD INSTITUTE, INC. · PI JESSE M ENGREITZ, RAJAT M GUPTA · 2023 to 2026
$2.7M
Identifying tobacco-genetic interactions through study of the aryl hydrocarbon receptor pathway.R01HL151535 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2021 to 2024
$2.7M
Molecular mechanisms of vascular calcification and their connection to coronary disease riskR01HL158525 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2022 to 2025
$2.4M
Mechanistic Studies of the Novel Human Coronary Artery Disease Gene SVEP1R01HL159171 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2022 to 2025
$2.2M
NCI NIH HHS P30 CA091842NHGRI NIH HHS R01 HG013371NHGRI NIH HHS U01 HG011762NHGRI NIH HHS UM1 HG008853NHGRI NIH HHS UM1 HG011972NHLBI NIH HHS R01 HL134817NHLBI NIH HHS R01 HL139478NHLBI NIH HHS R01 HL151535NHLBI NIH HHS R01 HL156846NHLBI NIH HHS R01 HL158525NHLBI NIH HHS R01 HL159171NHLBI NIH HHS R01 HL159176NHLBI NIH HHS R01 HL164811NHLBI NIH HHS R01 HL171045
6 · The paper itself

Abstract

Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most disease-associated variants lie within non-coding regions of the genome, rendering it difficult to determine the downstream causal gene and cell type. Here, we performed paired single nucleus gene expression and chromatin accessibility profiling from 44 human coronary arteries. To link disease variants to molecular traits, we developed a meta-map of 88 samples and discovered 11,182 single-cell chromatin accessibility quantitative trait loci (caQTLs). Heritability enrichment analysis and disease variant mapping demonstrated that smooth muscle cells (SMCs) harbor the greatest genetic risk for CAD. To capture the continuum of SMC cell states in disease, we used dynamic single cell caQTL modeling for the first time in tissue to uncover QTLs whose effects are modified by cell state and expand our insight into genetic regulation of heterogenous cell populations. Notably, we identified a variant in the

Indexed as

coronary artery diseaseCRISPR interferencegenome wide association studiesHi-Chuman geneticsquantitative trait loci (QTL)single cell ATAC sequencingsingle cell RNA sequencing

Identifiers

PMID39606421
PMCPMC11601770

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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.