| Title: | The risk stratification and predictive performance of a new combined polygenic risk score for hepatocellular carcinoma |
| Journal: | Journal of Gastroenterology |
| Published: | 10 Aug 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39126459/ |
| DOI: | https://doi.org/10.1007/s00535-024-02144-5 |
Publication 12990
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Abstract
BackgroundRecent genome-wide association studies (GWASs) in liver diseases have generated some polygenic risk scores (PRSs), but their predictive effectiveness on hepatocellular carcinoma (HCC) risk assessment remains unclear.MethodsHere, we constructed a novel combined polygenic risk score and evaluated its increment to the well-established risk model. We used 15 HCC-associated genetic loci from two PRSs and FinnGen GWAS data to calculate a PRS-combined score and to fit the related PRS model in the UK Biobank cohort (N = 436,162). The PRS-combined score was further assessed for risk stratification for HCC integrating with the recommended clinical risk scores.ResultsThe PRS-combined model achieved a better AUC (0.657) than that of PRS-HFC (0.637) and PRS-cirrhosis (0.645). The top 20% of the PRS-combined distribution had a 3.25 increased risk of HCC vs. the middle decile (45-55%). At the population level, the addition of PRS-combined to the CLivD score significantly increased the C-statistic (from 0.716 to 0.746) and provided a remarkable improvement in reclassification (NRI = 0.088) at the 10-year risk threshold of 0.2%. In clinic, additional assessment of PRS-combined would reclassify 34,647 intermediate-risk participants as high genetic risk, corresponding to an increase of 63.92% (62/97) of the HCC events classified at high risk using the Fibrosis-4 alone.ConclusionsThe PRS may enhance HCC risk prediction effectiveness in the general population and refine risk stratification of the conventional clinical indicator.</p>
10 Authors
- Chengxiao Yu
- Yuchen Tang
- Maojie Liu
- Xin Xu
- Xinyuan Ge
- Hongxia Ma
- Guangfu Jin
- Hongbing Shen
- Ci Song
- Zhibin Hu
1 Application
| Application ID | Title |
|---|---|
| 85248 | The interaction effects of genetic susceptibility and life exposures on human metabolomics and liver diseases risk and related mortality |
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