SynthesisAtherosclerosis2012
Genetic determinants of the ankle-brachial index: a meta-analysis of a cardiovascular candidate gene 50K SNP panel in the candidate gene association resource (CARe) consortium.
Synthesis in Atherosclerosis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Global vascular guidelines on the management of chronic limb-threatening ischemia.Journal of vascular surgery · 2019Guideline
- Genome-Wide Association Study of Genetic Variants Associated with Lower Extremity Amputation Risk in Peripheral Artery Disease.International journal of molecular sciences · 2026Article
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- Racial and Socioeconomic Health Disparities in Peripheral Artery Disease.Journal of the American Heart Association · 2024Review
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- Unveiling the Genetic Footprint: Exploring Somatic Mutations in Peripheral Arterial Disease Progression.Biomedicines · 2023Review
- Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease.International journal of molecular sciences · 2022Review
- The Genetic Architecture of the Etiology of Lower Extremity Peripheral Artery Disease: Current Knowledge and Future Challenges in the Era of Genomic Medicine.International journal of molecular sciences · 2022Review
- Unsupervised Learning for Automated Detection of Coronary Artery Disease Subgroups.Journal of the American Heart Association · 2021Article
- Wnt Pathway Gene Expression Is Associated With Arterial Stiffness.Journal of the American Heart Association · 2020Article
- Variants Associated with the Ankle Brachial Index Differ by Hispanic/Latino Ethnic Group: a genome-wide association study in the Hispanic Community Health Study/Study of Latinos.Scientific reports · 2019Article
- Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia.European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery · 2019Article
- Peripheral Arterial Disease Genetics: Progress to Date and Challenges Ahead.Current cardiology reports · 2017Review
- Peripheral artery disease: epidemiology and global perspectives.Nature reviews. Cardiology · 2017Review
- Peripheral Artery Disease and Aortic Disease.Global heart · 2016Review
- The genetic basis of peripheral arterial disease: current knowledge, challenges, and future directions.Circulation research · 2015Review
- Cryptic relatedness in epidemiologic collections accessed for genetic association studies: experiences from the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study and the National Health and Nutrition Examination Surveys (NHANES).Frontiers in genetics · 2015Article
- SNPflow: a lightweight application for the processing, storing and automatic quality checking of genotyping assays.PloS one · 2013Article
Corrections and comments
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Authors and funding
61 authors at 20 institutions in 5 countries.
Funding
Abstract
backgroundCandidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of ∼50,000 SNPs across ∼2100 candidate genes to identify genetic variants for ABI. METHODS AND
resultsWe studied subjects of European ancestry from 8 studies (n=21,547, 55% women, mean age 44-73 years) and African American ancestry from 5 studies (n=7267, 60% women, mean age 41-73 years) involved in the candidate gene association resource (CARe) consortium. In each ethnic group, additive genetic models were used (with each additional copy of the minor allele corresponding to the given beta) to test each SNP for association with continuous ABI (excluding ABI>1.40) and PAD (defined as ABI<0.90) using linear or logistic regression with adjustment for known PAD risk factors and population stratification. We then conducted a fixed-effects inverse-variance weighted meta-analyses considering a p<2×10(-6) to denote statistical significance.
resultsIn the European ancestry discovery meta-analyses, rs2171209 in SYTL3 (β=-0.007, p=6.02×10(-7)) and rs290481 in TCF7L2 (β=-0.008, p=7.01×10(-7)) were significantly associated with ABI. None of the SNP associations for PAD were significant, though a SNP in CYP2B6 (p=4.99×10(-5)) was among the strongest associations. These 3 genes are linked to key PAD risk factors (lipoprotein(a), type 2 diabetes, and smoking behavior, respectively). We sought replication in 6 population-based and 3 clinical samples (n=15,440) for rs290481 and rs2171209. However, in the replication stage (rs2171209, p=0.75; rs290481, p=0.19) and in the combined discovery and replication analysis the SNP-ABI associations were no longer significant (rs2171209, p=1.14×10(-3); rs290481, p=8.88×10(-5)). In African Americans, none of the SNP associations for ABI or PAD achieved an experiment-wide level of significance.
conclusionsGenetic determinants of ABI and PAD remain elusive. Follow-up of these preliminary findings may uncover important biology given the known gene-risk factor associations. New and more powerful approaches to PAD gene discovery are warranted.
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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.