A team at Wuhan Asia Heart Hospital applies bi-directional two-sample Mendelian randomization on GWAS data from FinnGen to uncover causal links between epigenetic clocks (IEAA, GrimAge, PhenoAge) and thromboembolism, highlighting key factors like PAI-1 and FGF23 in clot formation.
Key points
- Intrinsic epigenetic age acceleration (IEAA) inversely associates with deep venous thrombosis of lower extremities (OR 0.963).
- Genetically predicted PAI-1 levels show a modest causal link to other arterial embolism and thrombosis (OR 1.0005).
- FGF23 elevation causally increases risk of lower extremity arterial thrombosis (OR 1.68) and other arterial embolism (OR 1.66).
- Reverse MR reveals portal vein thrombosis decelerates PhenoAge and venous thromboembolism accelerates GrimAge metrics.
- Analyses employ IVW, weighted median/mode, MR-Egger and sensitivity tests (Cochran’s Q, MR-PRESSO, leave-one-out) to rule out pleiotropy.
Why it matters: This study leverages Mendelian randomization to move beyond correlations and establish genetic causality between epigenetic aging biomarkers and thromboembolic disease. Identifying molecules like PAI-1 and FGF23 as drivers of clot formation opens avenues for targeted prevention and personalized risk prediction in cardiovascular aging.
Q&A
- What is an epigenetic clock?
- How does Mendelian randomization work?
- Why are PAI-1 and FGF23 important?
- What is inverse variance-weighted analysis?
