A novel Bayesian fine-mapping model using a continuous global-local shrinkage prior with applications in prostate cancer analysis

The aim of fine-mapping is to identify genetic variants causally contributing to complex traits or diseases. Existing fine-mapping methods employ discrete Bayesian mixture priors and depend on a pre-specified maximum number of causal variants which may lead to sub-optimal solutions. In this work, we propose a novel fine-mapping method called h2-D2, utilizing a continuous global-local shrinkage prior. We also present an approach to define credible sets of causal variants in continuous prior settings. Simulation studies demonstrate that h2-D2 outperforms the state-of-art fine-mapping methods such as SuSiE and FINEMAP in accurately identifying causal variants and estimating their effect sizes. We further applied h2-D2 to prostate cancer analysis and discovered some previously unknown causal variants. In addition, we inferred 385 target genes associated with the detected causal variants and several pathways that were significantly over-represented by these genes, shedding light on their potential roles in prostate cancer development and progression.