Varicose veins of lower extremities: Insights from the first large-scale genetic study

by Alexandra S. Shadrina, Sodbo Z. Sharapov, Tatiana I. Shashkova, Yakov A. Tsepilov 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 ide ntified the 12 reliably associated loci that explain 13% of the SNP-based heritability, and prioritized the most likely causal genesCASZ1,PIEZO1,PPP3R1,EBF1,STIM2,HFE,GATA2,NFATC2, andSOX9. 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 a...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research