A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia
Abstract Benign prostatic hyperplasia (BPH) is a prevalent urinary system disorder. Despite evidence of a significant genetic component from previous studies, the specific pathogenic genes and biological mechanisms are still largely unknown. The study utilized the FinnGen R10 dataset, encompassing 1...
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Nature Portfolio
2025-01-01
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| author | Li Wang Si-yu Chen Jian-wei Yang Kang-yu Wang Kun-peng Li Shun Wan Xiao-ran Li Li Yang |
| author_facet | Li Wang Si-yu Chen Jian-wei Yang Kang-yu Wang Kun-peng Li Shun Wan Xiao-ran Li Li Yang |
| author_sort | Li Wang |
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| description | Abstract Benign prostatic hyperplasia (BPH) is a prevalent urinary system disorder. Despite evidence of a significant genetic component from previous studies, the specific pathogenic genes and biological mechanisms are still largely unknown. The study utilized the FinnGen R10 dataset, encompassing 177,901 individuals (36,601 cases and 141,300 controls), and the GTEx v8 EQTLs files to conduct single-tissue and cross-tissue transcriptome-wide association studies (TWAS). FUSION method was utilized to validate the findings in specific tissues. Gene Analysis and Multi-marker Analysis of Genomic Annotation (MAGMA) were used to identify potential susceptibility genes. The intersection genes of the above results were analyzed by Mendelian randomization (MR), summary data-based MR (SMR) and colocalization studies. Fine-mapping of causal gene sets (FOCUS) software was employed to accurately locate risk genes. Gene Expression Omnibus (GEO) analysis explores the differential expression of genes. Finally, The GeneMANIA tool was utilized to further understand the functional roles of these susceptibility genes. The cross-tissue TWAS analysis revealed 28 genes associated with BPH susceptibility. Single-tissue TWAS and MAGMA further refined eight genes, and subsequent MR, SMR, FOCUS and colocalization analysis pinpointed INO80B as the key gene. The differential expression of this result was verified by GEO. INO80B may help prevent excessive prostatic cell proliferation by regulating cell cycle-related gene expression. Our research identified the INO80B gene, whose predicted expression is associated with BPH risk and hence provided a new insight into the genetic basis of this disease. However, further functional studies are necessary to elucidate the potential biological activity of these significant signals. |
| format | Article |
| id | doaj-art-aa28e1e1ede74eed81f3b865e3b2ee0d |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-aa28e1e1ede74eed81f3b865e3b2ee0d2025-01-26T12:25:27ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-87651-yA cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasiaLi Wang0Si-yu Chen1Jian-wei Yang2Kang-yu Wang3Kun-peng Li4Shun Wan5Xiao-ran Li6Li Yang7Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou UniversityAbstract Benign prostatic hyperplasia (BPH) is a prevalent urinary system disorder. Despite evidence of a significant genetic component from previous studies, the specific pathogenic genes and biological mechanisms are still largely unknown. The study utilized the FinnGen R10 dataset, encompassing 177,901 individuals (36,601 cases and 141,300 controls), and the GTEx v8 EQTLs files to conduct single-tissue and cross-tissue transcriptome-wide association studies (TWAS). FUSION method was utilized to validate the findings in specific tissues. Gene Analysis and Multi-marker Analysis of Genomic Annotation (MAGMA) were used to identify potential susceptibility genes. The intersection genes of the above results were analyzed by Mendelian randomization (MR), summary data-based MR (SMR) and colocalization studies. Fine-mapping of causal gene sets (FOCUS) software was employed to accurately locate risk genes. Gene Expression Omnibus (GEO) analysis explores the differential expression of genes. Finally, The GeneMANIA tool was utilized to further understand the functional roles of these susceptibility genes. The cross-tissue TWAS analysis revealed 28 genes associated with BPH susceptibility. Single-tissue TWAS and MAGMA further refined eight genes, and subsequent MR, SMR, FOCUS and colocalization analysis pinpointed INO80B as the key gene. The differential expression of this result was verified by GEO. INO80B may help prevent excessive prostatic cell proliferation by regulating cell cycle-related gene expression. Our research identified the INO80B gene, whose predicted expression is associated with BPH risk and hence provided a new insight into the genetic basis of this disease. However, further functional studies are necessary to elucidate the potential biological activity of these significant signals.https://doi.org/10.1038/s41598-025-87651-yBPHTWASUTMOSTGeneMendelian randomization |
| spellingShingle | Li Wang Si-yu Chen Jian-wei Yang Kang-yu Wang Kun-peng Li Shun Wan Xiao-ran Li Li Yang A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia Scientific Reports BPH TWAS UTMOST Gene Mendelian randomization |
| title | A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia |
| title_full | A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia |
| title_fullStr | A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia |
| title_full_unstemmed | A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia |
| title_short | A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia |
| title_sort | cross tissue transcriptome wide association study identifies new susceptibility genes for benign prostatic hyperplasia |
| topic | BPH TWAS UTMOST Gene Mendelian randomization |
| url | https://doi.org/10.1038/s41598-025-87651-y |
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