Interactive and evolutionary effect of CASZ1 gene variants on varicose veins susceptibility in South Asian Indians

Three CASZ1 variants rs72860191 (OR 1.58, 95% CI 1.07-2.32, p = 0.01), rs7519604 (OR 1.43, 95% CI 1.05-1.94, p = 0.01), and rs11121615 (OR 0.69, 95% CI 0.50-0.95, p = 0.02) were observed to be significantly associated with VV. Haplotype analysis identified unique haplotype structure of South Asian Indians compared to other global populations. Moreover, the cumulative OR was observed to be higher than the independently estimated values (OR = 2.41, 95% CI 1.48-3.94), indicating genotypic epistasis of VV associated variants. The neutrality tests revealed balancing selection within CASZ1 in the studied population compared to other populations, CONCLUSION: The present study identified CASZ1 variants and their epistatic interactions is associated with VV susceptibility supported with evidence of balancing selection, provides crucial insights into the genetic architecture of VV in studied group, highlighting the impact of evolutionary forces on disease susceptibility.