Journal article

Large-scale transcriptome-wide association study identifies new prostate cancer risk regions.

Nicholas Mancuso, Simon Gayther, Alexander Gusev, Wei Zheng, Kathryn L Penney, Zsofia Kote-Jarai, Rosalind Eeles, Matthew Freedman, Christopher Haiman, Bogdan Pasaniuc, undefined PRACTICAL consortium

Nat Commun | Published : 2018

Abstract

Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have identified more than 100 risk regions, most of the risk genes at these regions remain largely unknown. Here we integrate the largest PrCa GWAS (N = 142,392) with gene expression measured in 45 tissues (N = 4458), including normal and tumor prostate, to perform a multi-tissue transcriptome-wide association study (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated with PrCa risk, 9 of which are regions with no genome-wide significant SNP within 2 Mb. 23 genes are significant in TWAS only for alternative splicing models in prostate tumor thus supporting the hypothesis of splicing driving..

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Grants

Awarded by U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)


Awarded by Medical Research Council


Awarded by Cancer Research UK


Awarded by NHGRI NIH HHS


Awarded by NCI NIH HHS


Awarded by U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)