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• W4225391725 abstract "Abstract Introduction Identifying disease-associated susceptibility loci is one of the most pressing and crucial challenges in modeling complex diseases. Existing approaches to biomarker discovery are subject to several limitations including underpowered detection, neglect for variant interactions, and restrictive dependence on prior biological knowledge. Addressing these challenges necessitates more ingenious ways of approaching the “missing heritability” problem. Objectives This study aims to discover disease-associated susceptibility loci by augmenting previous genome-wide association study (GWAS) using the integration of random forest and cluster analysis. Methods The proposed integrated framework is applied to a hepatitis B virus surface antigen (HBsAg) seroclearance GWAS data. Multiple cluster analyses were performed on (1) single nucleotide polymorphisms (SNPs) considered significant by GWAS and (2) SNPs with the highest feature importance scores obtained using random forest. The resulting SNP-sets from the cluster analyses were subsequently tested for trait-association. Results Three susceptibility loci possibly associated with HBsAg seroclearance were identified: (1) SNP rs2399971, (2) gene LINC00578, and (3) locus 11p15. SNP rs2399971 is a biomarker reported in the literature to be significantly associated with HBsAg seroclearance in patients who had received antiviral treatment. The latter two loci are linked with diseases influenced by the presence of hepatitis B virus infection. Conclusion These findings demonstrate the potential of the proposed integrated framework in identifying disease-associated susceptibility loci. With further validation, results herein could aid in better understanding complex disease etiologies and provide inputs for a more advanced disease risk assessment for patients." @default.
• W4225391725 created "2022-05-05" @default.
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• W4225391725 date "2022-04-28" @default.
• W4225391725 modified "2023-09-27" @default.
• W4225391725 title "A machine learning-based SNP-set analysis approach for identifying disease-associated susceptibility loci" @default.
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• W4225391725 doi "https://doi.org/10.1101/2022.04.25.22274157" @default.
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