Abstract
The genetic basis of phenotypic emergence provides valuable information for assessing individual risk. While association studies have been pivotal in identifying genetic risk factors within a population, complementing it with insights derived from predictions studies that assess individual-level risk offers a more comprehensive approach to understanding phenotypic expression. In this study, we established personalized risk assessment models using single-nucleotide polymorphism (SNP) data from 200 Korean patients, of which 100 experienced hepatitis B surface antigen (HBsAg) seroclearance and 100 patients demonstrated high levels of HBsAg. The risk assessment models determined the predictive power of the following: (1) genome-wide association study (GWAS)-identified candidate biomarkers considered significant in a reference study and (2) machine learning (ML)-identified candidate biomarkers with the highest feature importance scores obtained by using random forest (RF). While utilizing all features yielded 64% model accuracy, using relevant biomarkers achieved higher model accuracies: 82% for 52 GWAS-identified candidate biomarkers, 71% for three GWAS-identified biomarkers, and 80% for 150 ML-identified candidate biomarkers. Findings highlight that the joint contributions of relevant biomarkers significantly influence phenotypic emergence. On the other hand, combining ML-identified candidate biomarkers into the pool of GWAS-identified candidate biomarkers resulted in the improved predictive accuracy of 90%, demonstrating the capability of ML as an auxiliary analysis to GWAS. Furthermore, some of the ML-identified candidate biomarkers were found to be linked with hepatocellular carcinoma (HCC), reinforcing previous claims that HCC can still occur despite the absence of HBsAg.