Evidence map›Paper›PMID 38545784›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2024

Evaluation of Plasma Biomarkers for Causal Association With Peripheral Artery Disease.

Pranav Sharma, Derek Klarin, Benjamin F Voight, Philip S Tsao, Michael G Levin, Scott M Damrauer

Open access · greenAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. 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
5.7field-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

9 citing papers in PubMed, 10 citations in OpenAlex.

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  7. SerumDiagnostics (Basel, Switzerland) · 2025
    Article
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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

6 authors at 5 institutions in 1 country.

Pranav SharmaDepartment of Surgery, Perelman School of Medicine (P.S., S.M.D.), University of Pennsylvania, Philadelphia.ORCID 0009-0008-6302-6052
Derek KlarinVeterans Affairs Palo Alto Healthcare System, CA (D.K., P.S.T.).ORCID 0000-0002-4636-5780
Benjamin F VoightDepartment of Genetics (B.F.V., S.M.D.), University of Pennsylvania, Philadelphia.ORCID 0000-0002-6205-9994
Philip S TsaoVeterans Affairs Palo Alto Healthcare System, CA (D.K., P.S.T.).ORCID 0000-0001-7274-9318
Michael G LevinDivision of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine (M.G.L.), University of Pennsylvania, Philadelphia.ORCID 0000-0002-9937-9932
Scott M DamrauerDepartment of Surgery, Perelman School of Medicine (P.S., S.M.D.), University of Pennsylvania, Philadelphia.
VA Palo Alto Health Care System · USPhiladelphia VA Medical Center · USTranslational Therapeutics (United States) · USUniversity City Science Center · USUniversity of Pennsylvania · US

Funding

Training Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0M
Functional Interrogation of T2D-associated genes in human stem cell-derived models and miceUM1DK126194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GRANT, STRUAN F A, KAESTNER, KLAUS H · 2020 to 2024
$8.8M
Precision Cardio-Metabolic Phenotyping for Genetic Discovery and Risk PredictionIK2CX001780 · VA · PHILADELPHIA VA MEDICAL CENTER · PI DAMRAUER, SCOTT MICHAEL · 2018 to 2023
–
CSRD VA IK2 CX001780NHLBI NIH HHS T32 HL007843NIDDK NIH HHS UM1 DK126194
6 · The paper itself

Abstract

backgroundHundreds of biomarkers for peripheral artery disease (PAD) have been reported in the literature; however, the observational nature of these studies limits causal inference due to the potential of reverse causality and residual confounding. We sought to evaluate the potential causal impact of putative PAD biomarkers identified in human observational studies through genetic causal inference methods.

methodsPutative circulating PAD biomarkers were identified from human observational studies through a comprehensive literature search based on terms related to PAD using PubMed, Cochrane, and Embase. Genetic instruments were generated from publicly available genome-wide association studies of circulating biomarkers. Two-sample Mendelian randomization was used to test the association of genetically determined biomarker levels with PAD using summary statistics from a genome-wide association study of 31 307 individuals with and 211 753 individuals without PAD in the Veterans Affairs Million Veteran Program and replicated in data from FinnGen comprised of 11 924 individuals with and 288 638 individuals without PAD.

resultsWe identified 204 unique circulating biomarkers for PAD from the observational literature, of which 173 were genetically instrumented using genome-wide association study results. After accounting for multiple testing (false discovery rate, <0.05), 10 of 173 (5.8%) biomarkers had significant associations with PAD. These 10 biomarkers represented categories including plasma lipoprotein regulation, lipid homeostasis, and protein-lipid complex remodeling. Observational literature highlighted different pathways including inflammatory response, negative regulation of multicellular organismal processes, and regulation of response to external stimuli.

conclusionsIntegrating human observational studies and genetic causal inference highlights several key pathways in PAD pathophysiology. This work demonstrates that a substantial portion of biomarkers identified in observational studies are not well supported by human genetic evidence and emphasizes the importance of triangulating evidence to understand PAD pathophysiology. Although the identified biomarkers offer insights into atherosclerotic development in the lower limb, their specificity to PAD compared with more widespread atherosclerosis requires further study.

Indexed as

BiomarkersGenome-Wide Association StudyMendelian Randomization AnalysisPeripheral Arterial DiseaseGenetic Predisposition to DiseaseHumansObservational Studies as TopicPolymorphism, Single NucleotidePredictive Value of TestsRisk FactorsBiomarkersbiomarkershuman geneticsperipheral artery disease

Identifiers

PMID38545784
PMCPMC11043009
OpenAlexW4393265787

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.