Background <p>Growing evidence indicates that cardiometabolic disorders increase the risk of calcific aortic valve stenosis (CAVS). However, the precise underlying mechanisms are not fully understood.</p> Objective <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p> Graphical abstract <p></p>

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Shared genetic links between cardiometabolic diseases and aortic valve calcification

  • KaiJian Zhang,
  • Yi Zhang,
  • JingHan Chu,
  • ZiAn Feng,
  • BuChun Zhang

摘要

Background

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

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Graphical abstract