A Bayesian hierarchical variable selection prior for pathway-based GWAS using summary statistics.

Abstract:

:While genome-wide association studies (GWASs) have been widely used to uncover associations between diseases and genetic variants, standard SNP-level GWASs often lack the power to identify SNPs that individually have a moderate effect size but jointly contribute to the disease. To overcome this problem, pathway-based GWASs methods have been developed as an alternative strategy that complements SNP-level approaches. We propose a Bayesian method that uses the generalized fused hierarchical structured variable selection prior to identify pathways associated with the disease using SNP-level summary statistics. Our prior has the flexibility to take in pathway structural information so that it can model the gene-level correlation based on prior biological knowledge, an important feature that makes it appealing compared to existing pathway-based methods. Using simulations, we show that our method outperforms competing methods in various scenarios, particularly when we have pathway structural information that involves complex gene-gene interactions. We apply our method to the Wellcome Trust Case Control Consortium Crohn's disease GWAS data, demonstrating its practical application to real data.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Yang Y,Basu S,Zhang L

doi

10.1002/sim.8442

subject

Has Abstract

pub_date

2020-03-15 00:00:00

pages

724-739

issue

6

eissn

0277-6715

issn

1097-0258

journal_volume

39

pub_type

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