Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors
Abstract Background The polygenic risk score (PRS) is used to predict the risk of developing common complex diseases or cancers using genetic markers. Although PRS is used in clinical practice to predict breast cancer risk, it is more accurate for Europeans than for non-Europeans because of the samp...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-024-09974-w |
| _version_ | 1797356003430236160 |
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| author | Joo Young Hong Jang Hee Han Seung Hwan Jeong Cheol Kwak Hyeon Hoe Kim Chang Wook Jeong |
| author_facet | Joo Young Hong Jang Hee Han Seung Hwan Jeong Cheol Kwak Hyeon Hoe Kim Chang Wook Jeong |
| author_sort | Joo Young Hong |
| collection | DOAJ |
| description | Abstract Background The polygenic risk score (PRS) is used to predict the risk of developing common complex diseases or cancers using genetic markers. Although PRS is used in clinical practice to predict breast cancer risk, it is more accurate for Europeans than for non-Europeans because of the sample size of training genome-wide association studies (GWAS). To address this disparity, we constructed a PRS model for predicting the risk of renal cell carcinoma (RCC) in the Korean population. Results Using GWAS analysis, we identified 43 Korean-specific variants and calculated the PRS. Subsequent to plotting receiver operating characteristic (ROC) curves, we selected the 31 best-performing variants to construct an optimal PRS model. The resultant PRS model with 31 variants demonstrated a prediction rate of 77.4%. The pathway analysis indicated that the identified non-coding variants are involved in regulating the expression of genes related to cancer initiation and progression. Notably, favorable lifestyle habits, such as avoiding tobacco and alcohol, mitigated the risk of RCC across PRS strata expressing genetic risk. Conclusion A Korean-specific PRS model was established to predict the risk of RCC in the underrepresented Korean population. Our findings suggest that lifestyle-associated factors influencing RCC risk are associated with acquired risk factors indirectly through epigenetic modification, even among individuals in the higher PRS category. |
| first_indexed | 2024-03-08T14:19:26Z |
| format | Article |
| id | doaj.art-a9a2bc9b547243aba21d259df1735379 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-08T14:19:26Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-a9a2bc9b547243aba21d259df17353792024-01-14T12:13:02ZengBMCBMC Genomics1471-21642024-01-0125111110.1186/s12864-024-09974-wPolygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factorsJoo Young Hong0Jang Hee Han1Seung Hwan Jeong2Cheol Kwak3Hyeon Hoe Kim4Chang Wook Jeong5Biomedical Research Institute, Seoul National University HospitalDepartment of Urology, Seoul National University HospitalDepartment of Urology, Seoul National University HospitalDepartment of Urology, Seoul National University HospitalDepartment of Urology, Seoul National University HospitalDepartment of Urology, Seoul National University HospitalAbstract Background The polygenic risk score (PRS) is used to predict the risk of developing common complex diseases or cancers using genetic markers. Although PRS is used in clinical practice to predict breast cancer risk, it is more accurate for Europeans than for non-Europeans because of the sample size of training genome-wide association studies (GWAS). To address this disparity, we constructed a PRS model for predicting the risk of renal cell carcinoma (RCC) in the Korean population. Results Using GWAS analysis, we identified 43 Korean-specific variants and calculated the PRS. Subsequent to plotting receiver operating characteristic (ROC) curves, we selected the 31 best-performing variants to construct an optimal PRS model. The resultant PRS model with 31 variants demonstrated a prediction rate of 77.4%. The pathway analysis indicated that the identified non-coding variants are involved in regulating the expression of genes related to cancer initiation and progression. Notably, favorable lifestyle habits, such as avoiding tobacco and alcohol, mitigated the risk of RCC across PRS strata expressing genetic risk. Conclusion A Korean-specific PRS model was established to predict the risk of RCC in the underrepresented Korean population. Our findings suggest that lifestyle-associated factors influencing RCC risk are associated with acquired risk factors indirectly through epigenetic modification, even among individuals in the higher PRS category.https://doi.org/10.1186/s12864-024-09974-wPolygenic risk scoreGenome-wide association studyRenal cell carcinomaKorean populationNon-coding variantEpigenetics |
| spellingShingle | Joo Young Hong Jang Hee Han Seung Hwan Jeong Cheol Kwak Hyeon Hoe Kim Chang Wook Jeong Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors BMC Genomics Polygenic risk score Genome-wide association study Renal cell carcinoma Korean population Non-coding variant Epigenetics |
| title | Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors |
| title_full | Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors |
| title_fullStr | Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors |
| title_full_unstemmed | Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors |
| title_short | Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors |
| title_sort | polygenic risk score model for renal cell carcinoma in the korean population and relationship with lifestyle associated factors |
| topic | Polygenic risk score Genome-wide association study Renal cell carcinoma Korean population Non-coding variant Epigenetics |
| url | https://doi.org/10.1186/s12864-024-09974-w |
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