Evidence map›Paper›PMID 24975946›Full record

ArticleAmerican journal of human genetics2014

Integrative DNA, RNA, and protein evidence connects TREML4 to coronary artery calcification.

Shurjo K Sen, Kimberly C Boelte, Jennifer J Barb, Roby Joehanes, XiaoQing Zhao, Qi Cheng, Lila Adams, Jamie K Teer, David S Accame, Soma Chowdhury and 22 more

Open access · greenAbstract readValidation Study
In one paragraph

Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. The biology of TREM receptors.Nature reviews. Immunology · 2023
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Frontiers in immunology · 2020
    Article
  12. Article
  13. Review
  14. Genetics of Subclinical Coronary Atherosclerosis.Current genetic medicine reports · 2018
    Article
  15. Article
  16. Article
  17. Genetics and Genomics of Coronary Artery Disease.Current cardiology reports · 2016
    Review
  18. Article
  19. Article
  20. 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

32 authors at 10 institutions in 2 countries.

Shurjo K SenNational Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Kimberly C BoelteNational Cancer Institute, NIH, Frederick, MD 21702, USA.
Jennifer J BarbCenter for Information Technology, NIH, Bethesda, MD 20892, USA.
Roby JoehanesCenter for Information Technology, NIH, Bethesda, MD 20892, USA.
XiaoQing ZhaoCVPath Institute, Gaithersburg, MD 20878, USA.
Qi ChengCVPath Institute, Gaithersburg, MD 20878, USA.
Lila AdamsCVPath Institute, Gaithersburg, MD 20878, USA.
Jamie K TeerMoffitt Cancer Center, Tampa, FL 33612, USA.
David S AccameNational Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Soma ChowdhuryCenter for Biologics Evaluation and Research, FDA, Bethesda, MD 20892, USA.
Larry N SinghNational Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
NISC Comparative Sequencing Program
CHARGE Consortium
Maryam KavousiNetherlands Genomics-Initiative-Sponsored Netherlands Consortium for Healthy Aging and Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
Patricia A PeyserDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48104, USA.
Laura QuigleyNational Cancer Institute, NIH, Frederick, MD 21702, USA.
Debra Long PrielApplied/Developmental Research Directorate, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Karen LauApplied/Developmental Research Directorate, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Douglas B KuhnsApplied/Developmental Research Directorate, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Teizo YoshimuraNational Cancer Institute, NIH, Frederick, MD 21702, USA.
Andrew D JohnsonCardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA; National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
Shih-Jen HwangCardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA; National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
Marcus Y ChenCardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
Andrew E AraiCardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
Eric D GreenNational Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
James C MullikinNational Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Frank D KolodgieCVPath Institute, Gaithersburg, MD 20878, USA.
Christopher J O'DonnellCardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA; National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
Renu VirmaniCVPath Institute, Gaithersburg, MD 20878, USA.
Peter J MunsonCenter for Information Technology, NIH, Bethesda, MD 20892, USA.
Daniel W McVicarNational Cancer Institute, NIH, Frederick, MD 21702, USA.
Leslie G BieseckerNational Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. Electronic address: lesb@mail.nih.gov.
National Human Genome Research Institute · USCVPath Institute · USNational Heart Lung and Blood Institute · USNational Cancer Institute · USCenter for Information Technology · USFrederick National Laboratory for Cancer Research · USCenter for Biologics Evaluation and Research · USErasmus MC · NLMoffitt Cancer Center · USUniversity of Michigan · US

Funding

Inter- and Intra-Species Comparative SequencingZIBHG000196 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI THOMAS, JAMES · 2009 to 2025
$177.6M
Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
Signal Transduction of Paired Inhibitory Receptors of NK Cells and MacrophagesZIABC010300 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MCVICAR, DANIEL W. · 2009 to 2025
$24.6M
Genomic Ascertainment - Molecular and Genetic AspectsZIAHG200359 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BIESECKER, LESLIE · 2009 to 2025
$19.7M
Comparative Genomics Unit ResearchZIAHG200330 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI MULLIKIN, JAMES C · 2009 to 2022
$17.9M
Genomic Ascertainment - Clinical and Behavioral AspectsZIAHG200387 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BIESECKER, LESLIE · 2013 to 2025
$15.5M
Genomic Epidemiology of Cardiovascular DiseaseZIAHL006002 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2009 to 2015
$8.0M
Cardiovascular CT ResearchZIAHL006138 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ARAI, ANDREW · 2011 to 2016
$7.3M
Statistical And Computational Methods For Gene Expression and Proteomic AnalysisZIACT000266 · CIT · CENTER FOR INFORMATION TECHNOLOGY · PI MUNSON, PETER J · 2009 to 2016
$4.2M
Gene Expression for Functional Genomics in Human PopulationsZIAHL006175 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.2M
Functional Genetic Variation Underlying Cardiovascular Genomic EpidemiologyZIAHL006173 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.0M
Bioinformatics and Analysis of Genomics High Throughput DataZIACT000277 · CIT · CENTER FOR INFORMATION TECHNOLOGY · PI BARB-SMITH, JENNIFER · 2014 to 2020
$1.2M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01-HC-25195
6 · The paper itself

Abstract

Coronary artery calcification (CAC) is a heritable and definitive morphologic marker of atherosclerosis that strongly predicts risk for future cardiovascular events. To search for genes involved in CAC, we used an integrative transcriptomic, genomic, and protein expression strategy by using next-generation DNA sequencing in the discovery phase with follow-up studies using traditional molecular biology and histopathology techniques. RNA sequencing of peripheral blood from a discovery set of CAC cases and controls was used to identify dysregulated genes, which were validated by ClinSeq and Framingham Heart Study data. Only a single gene, TREML4, was upregulated in CAC cases in both studies. Further examination showed that rs2803496 was a TREML4 cis-eQTL and that the minor allele at this locus conferred up to a 6.5-fold increased relative risk of CAC. We characterized human TREML4 and demonstrated by immunohistochemical techniques that it is localized in macrophages surrounding the necrotic core of coronary plaques complicated by calcification (but not in arteries with less advanced disease). Finally, we determined by von Kossa staining that TREML4 colocalizes with areas of microcalcification within coronary plaques. Overall, we present integrative RNA, DNA, and protein evidence implicating TREML4 in coronary artery calcification. Our findings connect multimodal genomics data with a commonly used clinical marker of cardiovascular disease.

Indexed as

CalcinosisBase SequenceCoronary VesselsDNADNA PrimersHEK293 CellsHumansProteinsQuantitative Trait LociReceptors, ImmunologicRNADNADNA PrimersProteinsReceptors, ImmunologicRNATREML4 protein, human

Identifiers

PMID24975946
PMCPMC4085627
OpenAlexW2023924471

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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.