Eliciting priors and relaxing the single causal variant assumption in colocalisation analyses

Horizontal integration of summary statistics from different GWAS traits can be used to evaluate evidence for their shared genetic causality. One popular method to do this is a Bayesian method, coloc, which is attractive in requiring only GWAS summary statistics and no linkage disequilibrium estimate...

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Bibliographic Details
Published in:PLoS genetics Vol. 16; no. 4; p. e1008720
Main Author: Wallace, Chris
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.04.2020
Public Library of Science (PLoS)
Subjects:
Bayesian analysis
Biology and Life Sciences
Causality
Computer programs
Genome-Wide Association Study - methods
Genome-Wide Association Study - standards
Genomes
Humans
Hypotheses
Linkage Disequilibrium
Medicine and Health Sciences
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Research and Analysis Methods
Sensitivity analysis
Software
Statistical analysis
ISSN:1553-7404, 1553-7390, 1553-7404
Online Access:Get full text
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Summary:Horizontal integration of summary statistics from different GWAS traits can be used to evaluate evidence for their shared genetic causality. One popular method to do this is a Bayesian method, coloc, which is attractive in requiring only GWAS summary statistics and no linkage disequilibrium estimates and is now being used routinely to perform thousands of comparisons between traits. Here we show that while most users do not adjust default software values, misspecification of prior parameters can substantially alter posterior inference. We suggest data driven methods to derive sensible prior values, and demonstrate how sensitivity analysis can be used to assess robustness of posterior inference. The flexibility of coloc comes at the expense of an unrealistic assumption of a single causal variant per trait. This assumption can be relaxed by stepwise conditioning, but this requires external software and an LD matrix aligned to study alleles. We have now implemented conditioning within coloc, and propose a new alternative method, masking, that does not require LD and approximates conditioning when causal variants are independent. Importantly, masking can be used in combination with conditioning where allelically aligned LD estimates are available for only a single trait. We have implemented these developments in a new version of coloc which we hope will enable more informed choice of priors and overcome the restriction of the single causal variant assumptions in coloc analysis.
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The authors have declared that no competing interests exist.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1008720