Shared genetic links between cardiometabolic diseases and aortic valve calcification

Growing evidence indicates that cardiometabolic disorders increase the risk of calcific aortic valve stenosis (CAVS). However, the precise underlying mechanisms are not fully understood.

This study aimed to establish a causal association between cardiometabolic diseases and CAVS by using genetic correlations and a bidirectional two-sample Mendelian randomization (MR) analysis.

Genome-wide association study (GWAS) data for seven cardiometabolic disorders and CAVS were obtained from the FinnGen consortium. The genetic correlations between two conditions were evaluated using the linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods. MR analyses were conducted with inverse-variance weighted (IVW) regression as the principal method, complemented by weighted median, heterogeneity analysis, and sensitivity tests.

We identified 12 shared genes between cardiometabolic disorders and CAVS. Functional enrichment analysis revealed that these overlapping genes are involved in cholesterol homeostasis, vascular remodeling, smooth muscle proliferation, and lipid accumulation. MR analysis suggested a causal relationship between cardiometabolic disorders and CAVS.

Our study indicates significant genetic overlap between cardiometabolic disorders and CAVS. This finding provides valuable insights into the underlying mechanisms of their co-occurrence and has important implications for future therapeutic strategies.

The online version contains supplementary material available at 10.1007/s12055-025-02090-8.