PT  - JOURNAL ARTICLE
AU  - Mancuso, Nicholas
AU  - Gayther, Simon
AU  - Gusev, Alexander
AU  - Zheng, Wei
AU  - Penney, Kathryn L.
ED - consortium the PRACTICAL, CRUK, BPC3, CAPS, PEGASUS
AU  - Kote-Jarai, Zsofia
AU  - Eeles, Rosalind
AU  - Freedman, Matthew
AU  - Haiman, Christopher
AU  - Pasaniuc, Bogdan
TI  - Large-scale transcriptome-wide association study identifies new prostate cancer risk regions
AID  - 10.1101/345736
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 345736
4099  - http://biorxiv.org/content/early/2018/06/14/345736.short
4100  - http://biorxiv.org/content/early/2018/06/14/345736.full
AB  - 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=4,458), including normal and tumor prostate, to perform a multi-tissue transcriptomewide association study (TWAS) for PrCa. We identify 235 genes at 87 independent 1Mb regions associated with PrCa risk, 9 of which are regions with no genome-wide significant SNP within 2Mb. 24 genes are significant in TWAS only for alternative splicing models in prostate tumor thus supporting the hypothesis of splicing driving risk for continued oncogenesis. Finally, we use a Bayesian probabilistic approach to estimate credible sets of genes containing the causal gene at pre-defined level; this reduced the list of 235 associations to 120 genes in the 90% credible set. Overall, our findings highlight the power of integrating expression with PrCa GWAS to identify novel risk loci and prioritize putative causal genes at known risk loci.