Transcriptome-wide association study identifies genes associated with bladder cancer risk
Abstract Genome-wide association studies (GWAS) have detected several susceptibility variants for urinary bladder cancer, but how gene regulation affects disease development remains unclear. To extend GWAS findings, we conducted a transcriptome-wide association study (TWAS) using PrediXcan to predic...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-85565-3 |
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| author | Siting Li Jiang Gui Margaret R. Karagas Michael N. Passarelli |
| author_facet | Siting Li Jiang Gui Margaret R. Karagas Michael N. Passarelli |
| author_sort | Siting Li |
| collection | DOAJ |
| description | Abstract Genome-wide association studies (GWAS) have detected several susceptibility variants for urinary bladder cancer, but how gene regulation affects disease development remains unclear. To extend GWAS findings, we conducted a transcriptome-wide association study (TWAS) using PrediXcan to predict gene expression levels in whole blood using genome-wide genotype data for 6180 bladder cancer cases and 5699 controls included in the database of Genotypes and Phenotypes (dbGaP). Logistic regression was used to estimate adjusted gene-level odds ratios (OR) per 1-standard deviation higher expression with 95% confidence intervals (CI) for bladder cancer risk. We further assessed associations for individual single-nucleotide polymorphisms (SNPs) used to predict expression levels and proximal loci for genes identified in gene-level analyses with false-discovery rate (FDR) correction. TWAS identified four genes for which expression levels were associated with bladder cancer risk: SLC39A3 (OR = 0.91, CI = 0.87–0.95, FDR = 0.015), ZNF737 (OR = 0.91, CI = 0.88–0.95, FDR = 0.016), FAM53A (OR = 1.09, CI = 1.05–1.14, FDR = 0.022), and PPP1R2 (OR = 1.09, CI = 1.05–1.13, FDR = 0.049). Findings from this TWAS enhance our understanding of how genetically-regulated gene expression affects bladder cancer development and point to potential prevention and treatment targets. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-c8407d075bca4b0f90cef0073f4c66012025-01-12T12:20:42ZengNature PortfolioScientific Reports2045-23222025-01-011511810.1038/s41598-025-85565-3Transcriptome-wide association study identifies genes associated with bladder cancer riskSiting Li0Jiang Gui1Margaret R. Karagas2Michael N. Passarelli3Department of Biomedical Data Science, Geisel School of Medicine at DartmouthDepartment of Biomedical Data Science, Geisel School of Medicine at DartmouthDepartment of Epidemiology, Geisel School of Medicine at DartmouthDepartment of Epidemiology, Geisel School of Medicine at DartmouthAbstract Genome-wide association studies (GWAS) have detected several susceptibility variants for urinary bladder cancer, but how gene regulation affects disease development remains unclear. To extend GWAS findings, we conducted a transcriptome-wide association study (TWAS) using PrediXcan to predict gene expression levels in whole blood using genome-wide genotype data for 6180 bladder cancer cases and 5699 controls included in the database of Genotypes and Phenotypes (dbGaP). Logistic regression was used to estimate adjusted gene-level odds ratios (OR) per 1-standard deviation higher expression with 95% confidence intervals (CI) for bladder cancer risk. We further assessed associations for individual single-nucleotide polymorphisms (SNPs) used to predict expression levels and proximal loci for genes identified in gene-level analyses with false-discovery rate (FDR) correction. TWAS identified four genes for which expression levels were associated with bladder cancer risk: SLC39A3 (OR = 0.91, CI = 0.87–0.95, FDR = 0.015), ZNF737 (OR = 0.91, CI = 0.88–0.95, FDR = 0.016), FAM53A (OR = 1.09, CI = 1.05–1.14, FDR = 0.022), and PPP1R2 (OR = 1.09, CI = 1.05–1.13, FDR = 0.049). Findings from this TWAS enhance our understanding of how genetically-regulated gene expression affects bladder cancer development and point to potential prevention and treatment targets.https://doi.org/10.1038/s41598-025-85565-3Bladder CancerTWASGWASCase-control |
| spellingShingle | Siting Li Jiang Gui Margaret R. Karagas Michael N. Passarelli Transcriptome-wide association study identifies genes associated with bladder cancer risk Scientific Reports Bladder Cancer TWAS GWAS Case-control |
| title | Transcriptome-wide association study identifies genes associated with bladder cancer risk |
| title_full | Transcriptome-wide association study identifies genes associated with bladder cancer risk |
| title_fullStr | Transcriptome-wide association study identifies genes associated with bladder cancer risk |
| title_full_unstemmed | Transcriptome-wide association study identifies genes associated with bladder cancer risk |
| title_short | Transcriptome-wide association study identifies genes associated with bladder cancer risk |
| title_sort | transcriptome wide association study identifies genes associated with bladder cancer risk |
| topic | Bladder Cancer TWAS GWAS Case-control |
| url | https://doi.org/10.1038/s41598-025-85565-3 |
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