A Bayesian fine-mapping model using a continuous global-local shrinkage prior with applications in prostate cancer analysis.
Am J Hum Genet
; 111(2): 213-226, 2024 02 01.
Article
in En
| MEDLINE
| ID: mdl-38171363
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Quantitative Trait Loci
Type of study:
Prognostic_studies
Limits:
Humans
/
Male
Language:
En
Journal:
Am J Hum Genet
Year:
2024
Type:
Article
Affiliation country:
China