Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities

Varicose veins of lower extremities (VVs) are a highly prevalent condition, the pathogenesis of which is still not fully elucidated. Mendelian randomization (MR) can provide useful preliminary information on the traits that are potentially causally related to the disease. The aim of the present study is to replicate the effects of the plasma levels of MHC class I polypeptide-related sequence B (MICB) and cluster of differentiation 209 (CD209) proteins reported in a previous hypothesis-free MR study. We conducted MR analysis using a fixed effects inverse-variance weighted meta-analysis of Wald ratios method. For MICB and CD209, we used data from a large-scale genome-wide association study (GWAS) for plasma protein levels (N = 3,301). For VVs, we used GWAS data obtained in the FinnGen project (N = 128,698), the eMERGE network (phase 3, N = 48,429), and the UK Biobank data available in the Gene ATLAS (N = 452,264). The data used in the study were obtained in individuals of European descent. The results for MICB did not pass criteria for statistical significance and replication. The results for CD209 passed all statistical significance thresholds, indicating that the genetically predicted increase in CD209 level is associated with increased risk of VVs (beta(MR) (SE) = 0.07 (0.01), OR (95% CI) = 1.08 (1.05-1.10), P-value = 5.9 x10(-11) in the meta-analysis of three cohorts). Our findings provide further support that CD209 can potentially be involved in VVs. In future studies, independent validation of our results using data from more powerful GWASs for CD209 measured by different methods would be beneficial.