Genetic associations in chronic hepatitis B infection: toward developing polygenic risk scores

Area of Science:

• Genetics and Genomics
• Hepatology
• Infectious Diseases

Background:

• Chronic hepatitis B (CHB) presents diverse clinical outcomes, necessitating improved risk stratification.
• Current models for predicting hepatocellular carcinoma and cirrhosis in CHB lack discriminatory power.
• A genetic-based tool is needed to enhance CHB patient risk assessment.

Purpose of the Study:

• To highlight genetic association studies identifying susceptibility loci for CHB.
• To propose the translation of CHB genetic loci into polygenic risk scores (PRS).
• To advocate for PRS as an adjunct to existing CHB outcome predictive models.

Main Methods:

• Review of genetic association studies implicating HLA and cytokine loci in CHB susceptibility.
• Conceptual advancement of translating identified genetic loci into polygenic risk scores.
• Discussion of challenges and future research directions in CHB genetics.

Main Results:

• Genetic association studies have identified specific HLA and cytokine loci linked to CHB susceptibility.
• Polygenic risk scores derived from these loci show potential for enhancing predictive accuracy.
• The need for improved genetic predictive models for CHB outcomes is evident.

Conclusions:

• Translating CHB genetic susceptibility loci into polygenic risk scores offers a promising enhancement to current predictive models.
• Future research must address current hurdles, including the need for greater genetic data diversity, particularly from sub-Saharan Africa.
• Integrating genetic information can significantly improve personalized risk stratification for patients with chronic hepatitis B.