An integrated germline and somatic genomic model for coronary artery disease - PubMed
5 hours ago
- #genomic-model
- #risk-prediction
- #coronary-artery-disease
- Developed an integrated genomic model combining six germline and somatic genetic drivers for coronary artery disease, including polygenic risk score and clonal hematopoiesis.
- Evaluated the model in UK Biobank (N=391,536) and validated in TOPMed (N=34,177), showing risk ranges from 1.1% to 15.5% in UK Biobank and 3.8% to 33.0% in TOPMed, with a stronger gradient in males.
- The model identifies high-risk individuals lacking single high-risk factors and low-risk individuals with known high-risk factors, and enhances the Pooled Cohort Equations in middle age.
- While offering modest predictive improvement over polygenic risk score at the population level, it detects about 13% of high-risk individuals missed by polygenic risk score alone.