Identification of potential genetic Loci and polygenic risk model for Budd-Chiari syndrome in Chinese population

Area of Science:

• Genetics
• Hepatology
• Vascular Biology

Background:

• Budd-Chiari syndrome (BCS) involves hepatic venous outflow obstruction with potentially life-threatening outcomes.
• Identifiable causes of BCS are often lacking, and etiological factors vary geographically.
• Understanding genetic predispositions is crucial for improving BCS risk prediction and management.

Purpose of the Study:

• To investigate the genetic underpinnings of Budd-Chiari syndrome (BCS).
• To develop and validate a polygenic risk scoring (PRS) model for BCS.
• To explore shared genetic risks between BCS, venous thromboembolism, and vascular malformations.

Main Methods:

• Whole-exome sequencing was performed on 500 BCS patients and 696 controls.
• Polygenic risk scoring (PRS) models were developed using PLINK, LASSOSUM, BLUP, and BayesA.
• Risk factors for venous thromboembolism and vascular malformations were assessed for predictive modeling.

Main Results:

• Potential BCS risk mutations, including rs1042331, were identified.
• The optimal BayesA-generated PRS model achieved an AUC >0.9 in an external cohort.
• Genetic risk differences between Eastern and Western populations were highlighted.

Conclusions:

• A validated PRS model offers a novel approach to BCS risk prediction.
• Shared genetic risks suggest interconnectedness between BCS, venous thromboembolism, and vascular malformations.
• Findings provide new insights into the complex pathogenesis of Budd-Chiari syndrome.