Replication Study Identified EFEMP1 Association with Varicose Vein Predisposition among Indians

Abstract

Background: Varicose veins are chronic condition that affects the lower extremities of the body. Several factors such as age, gender, weight, height, prolonged sitting or standing time are associated with this trait. Recently, genome wide studies have identifying genetic biomarkers that are associated with varicose veins in different ethnic groups. Such genetic studies are lacking in South Asians specifically in Indians where prevalence of varicose veins is high and it is important to replicate these variants in stated population. The aim of study is to replicate the association of genetic variants associated with varicose veins which were found to be associated in the other ethnic groups. Methodology: The studied cohort is of Indian population comprising of unrelated 104 varicose veins cases and 448 non-VV controls. The samples were genotyped using the Illumina Global Screening Array. Using the genomic data from UK BioBank and 23andMe studied cohorts; eight genetic variants were selected to replicate in our dataset. Allelic association was performed to identify the effective allele and risk was estimated using odds ratio and p value as level of significance. Multifactor Dimensionality Reduction was used to estimate the cumulative effect of variants in Indians. Result: Variant rs3791679 of EFEMP1 was found to be associated with varicose veins in Indians. After observing the association of EFEMP1 with varicose veins, we further ensued to identify all genetic variants within EFEMP1 to uncover the additional variants associated with this trait. Interestingly, we identified six new variants of EFEM1 gene that have shown association. Moreover, the cumulative effect of all associated variations was estimated and the risk was 2.7 times higher in cases than controls whereas independently their effect is ranging from 0.37–1.58. Conclusion: In this study, EFEMP1 was identified as a potential gene related with the risk of varicose veins in Indians. Present study also highlights that evaluating the maximum number of variants of a gene rather than focusing solely on replicating single variations offers a more comprehensive and nuanced understanding of the genetic factors contributing to a complex trait like varicose veins.