Shared genetic associations between CHA2DS2-VASc score and cardio-embolic stroke: Insights from mendelian randomization based bioinformatics analysis

Abstract

The CHA₂DS₂-VASc score is a risk assessment score to predict cardio-embolic stroke (CES), suggesting shared genetic susceptibility. This study aimed to explore the shared genetic association of genetically predicted CHA₂DS₂-VASc score and CES using multiple analytic frameworks. We conducted a comprehensive analysis of genetic data from 13 traits of CHA₂DS₂-VASc score and CES using summary statistics from large-scale genome-wide association studies (GWAS). We employed statistical methods such as linkage disequilibrium score regression (LDSC), cross-trait analysis, bidirectional Mendelian randomization, colocalization analysis and gene-based association analysis to explore genetic correlations and identify pleiotropic single nucleotide polymorphisms (SNPs) and shared genes. LDSC and Mendelian randomization analysis revealed a significant genetic correlation between CHA₂DS₂-VASc score and CES. Cross-trait and colocalization analysis identified 9 potential loci and 13 significant independent SNPs. Gene-based association analysis reported 9 genes significant across at least three methods, with IL6R being the shared gene identified by all four methods, highlighting potential shared biological mechanisms involving immune responses and inflammatory activities. In conclusion, our study revealed shared genetic associations between the genetically predicted CHA₂DS₂-VASc score and CES, which was supported by causal relationship, shared loci, and genetic correlation analyses.