A Splicing Transcriptome-Wide Association Study Identifies Candidate Altered Splicing for Prostate Cancer Risk.
OMICS
; 27(8): 372-380, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-37486714
ABSTRACT
Prostate cancer (PCa) represents a huge public health burden among men. Many susceptibility genetic factors for PCa still remain unknown. In this study, we performed a large splicing transcriptome-wide association study (spTWAS) using three modeling strategies to develop alternative splicing genetic prediction models for identifying novel susceptibility loci and splicing introns for PCa risk by assessing 79,194 cases and 61,112 controls of European ancestry in the PRACTICAL, CRUK, CAPS, BPC3, and PEGASUS consortia. We identified 120 splicing introns of 97 genes showing an association with PCa risk at false discovery rate (FDR)-corrected threshold (FDR <0.05). Of them, 33 genes were enriched in PCa-related diseases and function categories. Fine-mapping analysis suggested that 21 splicing introns of 19 genes were likely causally associated with PCa risk. Thirty-five splicing introns of 34 novel genes were identified to be related to PCa susceptibility for the first time, and 11 of the genes were enriched in a cancer-related network. Our study identified novel loci and splicing introns associated with PCa risk, which can improve our understanding of the etiology of this common malignancy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Transcriptoma
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article