Top SNPs from the phenome-wide association study catalog and the risk of varicose veins of lower extremities: A replication study

Varicose veins are the most common venous pathology of lower limbs. A strong body of evidence indicates a prominent role of heredity in the development of this condition, but genetic factors influencing its risk are still poorly investigated. Phenome-wide association study (PheWAS) is a novel approach to discovering associations between genetic polymorphism and multiple phenotypes. The results of the largest PheWAS today are included in the PheWAS catalog, which contains the associations with a variety of phenotypes including varicose veins of lower extremities. In our study we aimed to replicate top 5 associations from the PheWAS catalog in the population of ethnic Russians. We determined the genotypes of polymorphisms rs735854, rs7023329, rs2857595, rs6420094, and rs16856202 in the sample of 460 patients with primary varicose veins of lower extremities and 646 control subjects without a history of chronic venous disease. Though we had enough statistical power to validate the reported associations, no evidence for statistical significant association was revealed in our study. We can speculate that either these polymorphisms have no effect on the risk of varicose veins, or their effects can be modulated by currently uninvestigated ethnic, environmental or lifestyle factors.