• Media type: E-Article
  • Title: Genetic fine-mapping from summary data using a nonlocal prior improves the detection of multiple causal variants
  • Contributor: Karhunen, Ville; Launonen, Ilkka; Järvelin, Marjo-Riitta; Sebert, Sylvain; Sillanpää, Mikko J
  • imprint: Oxford University Press (OUP), 2023
  • Published in: Bioinformatics
  • Language: English
  • DOI: 10.1093/bioinformatics/btad396
  • ISSN: 1367-4811
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec><jats:title>Motivation</jats:title><jats:p>Genome-wide association studies (GWAS) have been successful in identifying genomic loci associated with complex traits. Genetic fine-mapping aims to detect independent causal variants from the GWAS-identified loci, adjusting for linkage disequilibrium patterns.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We present “FiniMOM” (fine-mapping using a product inverse-moment prior), a novel Bayesian fine-mapping method for summarized genetic associations. For causal effects, the method uses a nonlocal inverse-moment prior, which is a natural prior distribution to model non-null effects in finite samples. A beta-binomial prior is set for the number of causal variants, with a parameterization that can be used to control for potential misspecifications in the linkage disequilibrium reference. The results of simulations studies aimed to mimic a typical GWAS on circulating protein levels show improved credible set coverage and power of the proposed method over current state-of-the-art fine-mapping method SuSiE, especially in the case of multiple causal variants within a locus.</jats:p></jats:sec><jats:sec><jats:title>Availability and implementation</jats:title><jats:p>https://vkarhune.github.io/finimom/.</jats:p></jats:sec>
  • Access State: Open Access