ArticlePLoS genetics2019
Varicose veins of lower extremities: Insights from the first large-scale genetic study.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- A multi-population phenome-wide association study of genetically-predicted height in the Million Veteran Program.PLoS genetics · 2022Pooled it
- Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities.PloS one · 2022Pooled it
- Increased vein wall thickness in Behçet's disease: from intravascular mechanical stress to vascular remodelling and venous thrombosis.Rheumatology international · 2026Review
- Sex-Specific Gene Expression Differences in Varicose Veins.Biomedicines · 2025Article
- Molecular Signatures Related to Inflammation and Angiogenesis in Patients with Lower Extremity Artery Disease, Abdominal Aortic Aneurysm, and Varicose Veins: Shared and Distinct Pathways.International journal of molecular sciences · 2025Article
- Endothelium Piezo1 deletion alleviates experimental varicose veins by attenuating perivenous inflammation.Molecular and cellular biochemistry · 2025Article
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- The Mechanobiological Hypothesis of Piezo Family-Mediated Exercise Intervention in Spinal Cord Injury Recovery.Neural plasticity · 2025Review
- Article
- Essential Roles of PIEZO1 in Mammalian Cardiovascular System: From Development to Diseases.Cells · 2024Review
- Exome sequencing identifies novel genetic variants associated with varicose veins.PLoS genetics · 2024Article
- 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2024Review
- Role of the CASZ1 transcription factor in tissue development and disease.European journal of medical research · 2023Review
- Efficacy and safety of ultrasound-guided foam sclerotherapy combined with endoluminal radiofrequency closure in patients with varicose veins of lower extremities.International wound journal · 2023Article
- Review
- Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.Circulation · 2023Review
- Molecular Determinants of Chronic Venous Disease: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Genome-wide association study of varicose veins identifies a protective missense variant in GJD3 enriched in the Finnish population.Communications biology · 2023Article
- Increased Expression of Tetraspanins, ALIX and HSP-70 in the Placenta Tissue of Women with Chronic Venous Disease during Pregnancy.International journal of medical sciences · 2023Article
- Factors associated with chronic venous disease: study in 1,136 patients treated for varicose veins of the lower limbs in a specialized clinic.Jornal vascular brasileiro · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Varicose veins of lower extremities (VVs) are a common multifactorial vascular disease. Genetic factors underlying VVs development remain largely unknown. Here we report the first large-scale study of VVs performed on a freely available genetic data of 408,455 European-ancestry individuals. We identified the 12 reliably associated loci that explain 13% of the SNP-based heritability, and prioritized the most likely causal genes CASZ1, PIEZO1, PPP3R1, EBF1, STIM2, HFE, GATA2, NFATC2, and SOX9. VVs-associated variants within these loci exhibited pleiotropic effects on several phenotypes including blood pressure/hypertension and blood cell traits. Gene set enrichment analysis revealed gene categories related to abnormal vasculogenesis. Genetic correlation analysis confirmed known epidemiological associations between VVs and deep venous thrombosis, weight, rough labor, and standing job, and found a genetic overlap with multiple traits that have not been previously suspected to share common genetic background with VVs. These traits included educational attainment, fluid intelligence and prospective memory scores, walking pace (negative correlation with VVs), smoking, height, number of operations, pain, and gonarthrosis (positive correlation with VVs). Finally, Mendelian randomization analysis provided evidence for causal effects of plasma levels of MICB and CD209 proteins, and anthropometric traits such as waist and hip circumference, height, weight, and both fat and fat-free mass. Our results provide novel insight into both VVs genetics and etiology. The revealed genes and proteins can be considered as good candidates for follow-up functional studies and might be of interest as potential drug targets.
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