作者
Nicholas Mancuso, Simon Gayther, Alexander Gusev, Wei Zheng, Kathryn L Penney, Zsofia Kote-Jarai, Rosalind Eeles, Matthew Freedman, Christopher Haiman, Bogdan Pasaniuc
发表日期
2018/10/4
期刊
Nature communications
卷号
9
期号
1
页码范围
4079
出版商
Nature Publishing Group UK
简介
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 risk for continued oncogenesis. Finally, we use a Bayesian probabilistic approach to estimate credible sets of genes containing the causal gene at a pre-defined level; this reduced the list of 217 …
引用总数
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