Evidence map›Paper›PMID 32781905›Full record

ArticleCirculation research2020

Integrative Genomic Analysis Reveals Four Protein Biomarkers for Platelet Traits.

Dong Heon Lee, Chen Yao, Arunoday Bhan, Thorsten Schlaeger, Joshua Keefe, Benjamin A T Rodriguez, Shih-Jen Hwang, Ming-Huei Chen, Daniel Levy, Andrew D Johnson

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

Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Of Pea Plants and Platelets.Circulation research · 2020
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Dong Heon LeeThe Framingham Heart Study, Framingham, MA (D.H.L., C.Y., J.K., B.A.T.R., S,-J.H., M.-H.C., D.L., A.D.J.).
Chen YaoThe Framingham Heart Study, Framingham, MA (D.H.L., C.Y., J.K., B.A.T.R., S,-J.H., M.-H.C., D.L., A.D.J.).
Arunoday BhanBoston Children's Hospital, Boston, MA (A.B., T.S.).
Thorsten SchlaegerBoston Children's Hospital, Boston, MA (A.B., T.S.).
Joshua KeefeThe Framingham Heart Study, Framingham, MA (D.H.L., C.Y., J.K., B.A.T.R., S,-J.H., M.-H.C., D.L., A.D.J.).
Benjamin A T RodriguezThe Framingham Heart Study, Framingham, MA (D.H.L., C.Y., J.K., B.A.T.R., S,-J.H., M.-H.C., D.L., A.D.J.).
Shih-Jen HwangPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute National Institutes of Health, Bethesda, MD (D.H.L., C.Y., J.K., B.A.T.R., S.-J.H., M.-H.C., D.L., A.D.J.).
Ming-Huei ChenThe Framingham Heart Study, Framingham, MA (D.H.L., C.Y., J.K., B.A.T.R., S,-J.H., M.-H.C., D.L., A.D.J.).
Daniel LevyThe Framingham Heart Study, Framingham, MA (D.H.L., C.Y., J.K., B.A.T.R., S,-J.H., M.-H.C., D.L., A.D.J.).
Andrew D JohnsonThe Framingham Heart Study, Framingham, MA (D.H.L., C.Y., J.K., B.A.T.R., S,-J.H., M.-H.C., D.L., A.D.J.).
National Heart Lung and Blood Institute · USBoston Children's Hospital · US

Funding

Framingham Project/LevyZIAHL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2009 to 2025
$51.1M
Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
TRANSFUSION BIOLOGY AND MEDICINET32HL066987 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI JOHN P MANIS · 2001 to 2026
$10.2M
Project-002U54DK110805 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ORKIN, STUART H, ZON, LEONARD IRA · 2016 to 2020
$5.9M
Framingham Project/LevyZ01HL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2008 to 2008
$1.1M
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
Intramural NIH HHS Z01 HL006001Intramural NIH HHS Z99 HL999999Intramural NIH HHS ZIA HL006001NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NHLBI NIH HHS T32 HL066987NIDDK NIH HHS U54 DK110805
6 · The paper itself

Abstract

rationaleMean platelet volume (MPV) and platelet count (PLT) are platelet measures that have been linked to cardiovascular disease (CVD) and mortality risk. Identifying protein biomarkers for these measures may yield insights into CVD mechanisms.

objectiveWe aimed to identify causal protein biomarkers for MPV and PLT among 71 CVD-related plasma proteins measured in FHS (Framingham Heart Study) participants. METHODS AND

resultsWe conducted integrative analyses of genetic variants associated with PLT/MPV with protein quantitative trait locus variants associated with plasma proteins followed by Mendelian randomization to infer causal relations of proteins for PLT/MPV. We also tested protein-PLT/MPV association in FHS participants. Using induced pluripotent stem cell-derived megakaryocyte clones that produce functional platelets, we conducted RNA-sequencing and analyzed expression differences between low- and high-platelet producing clones. We then performed small interfering RNA gene knockdown experiments targeting genes encoding proteins with putatively causal platelet effects in megakaryocyte clones to examine effects on platelet production. In protein-trait association analyses, ten proteins were associated with MPV and 31 with PLT. Mendelian randomization identified 4 putatively causal proteins for MPV and 4 for PLT. GP-5 (Glycoprotein V), GRN (granulin), and MCAM (melanoma cell adhesion molecule) were associated with PLT, while MPO (myeloperoxidase) showed significant association with MPV in both analyses. RNA-sequencing analysis results were directionally concordant with observed and Mendelian randomization-inferred associations for GP-5, GRN, and MCAM. In siRNA gene knockdown experiments, silencing GP-5, GRN, and MPO decreased PLTs. Genome-wide association study results suggest several of these may be linked to CVD risk.

conclusionsWe identified 4 proteins that are causally linked to PLTs. These proteins may also have roles in the pathogenesis of CVD via a platelet/blood coagulation-based mechanism.

Indexed as

GranulinsMean Platelet VolumePeroxidasePlatelet CountPlatelet Membrane GlycoproteinsBiomarkersBlood ProteinsCardiovascular DiseasesCD146 AntigenCell DifferentiationFemaleGene SilencingGenome-Wide Association StudyHumansLongitudinal StudiesMaleBiomarkersBlood ProteinsCD146 AntigenGranulinsMCAM protein, humanMPO protein, humanPeroxidasePlatelet Membrane GlycoproteinsRNA, Small Interferingbiomarkerscardiovascular diseasesgeneticsmegakaryocytesproteomics

Identifiers

PMID32781905
PMCPMC8411925
OpenAlexW3048367177

What OpenQuestion holds

Textmetadata
LicenceTDM
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.