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Bayesian multivariant fine mapping using the Laplace prior.

Kevin Walters1, Hannuun Yaacob1,2

  • 1School of Mathematics and Statistics, University of Sheffield, Sheffield, UK.

Genetic Epidemiology
|February 5, 2023
PubMed
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The Laplace prior improves Bayesian fine-mapping by ranking genetic variants more effectively than the Gaussian prior. This method enhances the identification of causal single nucleotide polymorphisms (SNPs) in genetic studies.

Keywords:
BayesianLaplace priorfine mappingmulti-SNP

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Area of Science:

  • Genetics
  • Statistical Genetics
  • Computational Biology

Background:

  • Bayesian fine-mapping is crucial for identifying causal variants in genetic studies.
  • The Gaussian prior is the standard for effect size priors in multi-single nucleotide polymorphism (SNP) analyses.
  • Alternative priors may offer improved performance in fine-mapping studies.

Purpose of the Study:

  • To introduce and evaluate the Laplace prior for Bayesian multi-SNP fine-mapping.
  • To compare the ranking performance of the Laplace prior against the Gaussian prior and FINEMAP.
  • To assess the utility of the Laplace prior in a large-scale genetic dataset.

Main Methods:

  • Implementation of the Laplace prior in Bayesian multi-SNP fine-mapping.
  • Comparison of posterior inclusion probability (PIP) rankings between Laplace and Gaussian priors.
  • Evaluation using simulation scenarios and reanalysis of iCOGS case-control data.

Main Results:

  • The Laplace prior demonstrated superior ranking performance compared to the Gaussian prior and FINEMAP in simulated scenarios.
  • The Laplace prior showed better worst-case scenario properties.
  • Differences in top-ranked SNPs were observed even in a large dataset (iCOGS) when using the Laplace prior versus the Gaussian prior.

Conclusions:

  • The Laplace prior is a viable and potentially superior alternative to the Gaussian prior for Bayesian fine-mapping.
  • Its improved ranking performance can aid in more accurate causal variant identification.
  • The Laplace prior offers advantages, particularly for moderately sized fine-mapping studies.