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

Am J Hum Genet. 2024 Feb 1;111(2):213-226. doi: 10.1016/j.ajhg.2023.12.007. Epub 2024 Jan 2.


The aim of fine mapping is to identify genetic variants causally contributing to complex traits or diseases. Existing fine-mapping methods employ Bayesian discrete 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 Bayesian 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 current state-of-the-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 369 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.

Keywords: causal variant; credible set; fine mapping; global-local shrinkage prior; prostate cancer; variable selection.

MeSH terms

  • Bayes Theorem
  • Computer Simulation
  • Genome-Wide Association Study / methods
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Prostatic Neoplasms* / genetics
  • Quantitative Trait Loci*