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Published on: October 21, 2017
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Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.
Marijana Vujkovic1,2,3, David E Kaplan1,4, Jonas Ghouse5,6,7
1Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Medrxiv : the Preprint Server for Health Sciences
|September 26, 2025
Summary
This study identified new genetic loci linked to cirrhosis and liver cancer (HCC), revealing genetic risk scores that predict disease progression and treatment responses in chronic liver disease (CLD) patients.
Area of Science:
- Genetics
- Hepatology
- Genomics
Background:
- Chronic liver disease (CLD) can lead to cirrhosis and hepatocellular carcinoma (HCC).
- Understanding the genetic factors influencing CLD progression is crucial for developing targeted therapies.
Purpose of the Study:
- To identify genetic loci associated with cirrhosis and HCC through a large-scale genome-wide association study (GWAS).
- To investigate the role of genetic variants in disease progression and treatment response in CLD patients.
Main Methods:
- Conducted a multi-ancestry GWAS for cirrhosis and HCC, including gene-burden analysis of whole-genome sequencing data.
- Utilized large cohorts for discovery and replication, analyzing genetic risk scores and treatment interactions.
Main Results:
- Identified 27 loci for cirrhosis (10 novel) and 11 for HCC (3 novel), with specific genes like FGF21, RPTOR, IFNL3/4, GSTA5, APOB, and ATP9B implicated.
- A high cirrhosis genetic risk score significantly increased the risk of CLD progression to cirrhosis and cirrhosis to HCC.
- Genetic variants modified treatment responses in chronic hepatitis C patients.
Conclusions:
- Uncovered novel genetic insights into the pathogenesis of cirrhosis and HCC.
- Demonstrated the clinical utility of genetic risk scores in predicting CLD progression.
- Highlighted the potential for personalized medicine approaches in managing CLD and its complications.
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