ArticleArteriosclerosis, thrombosis, and vascular biology2024
Evaluation of Plasma Biomarkers for Causal Association With Peripheral Artery Disease.
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.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Potential Role of Circulating Biomarkers in Peripheral Artery Disease.Current cardiology reports · 2026Review
- Causal inference and digital twins: a roadmap for the future of clinical trials.NPJ digital medicine · 2026Review
- Indoleacrylic acid mitigates vascular rarefaction and enhances ischemia-induced neovascularization in aging via APLNR signaling.Acta pharmacologica Sinica · 2026Article
- Obstructive Sleep Apnea and Hypercoagulability: Combining Observational and Mendelian Randomization Analyses to Explore Causal Relationships.Nature and science of sleep · 2026Article
- Variant-to-Biomarker Pathways in Peripheral Artery Disease: Multiomics Integration and Clinical Translation.Human mutation · 2026Review
- Alcohol, Liver Disease, and Peripheral Arterial Disease: Epidemiology, Mechanisms, and Clinical Implications.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- SerumDiagnostics (Basel, Switzerland) · 2025Article
- Article
- The functions of apolipoproteins and lipoproteins in health and disease.Molecular biomedicine · 2024Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
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.
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Registered trials
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.