Dataset Information

An approximate Bayesian significance test for genomic evaluations.

ABSTRACT: Genomic information can be used to study the genetic architecture of some trait. Not only the size of the genetic effect captured by molecular markers and their position on the genome but also the mode of inheritance, which might be additive or dominant, and the presence of interactions are interesting parameters. When searching for interacting loci, estimating the effect size and determining the significant marker pairs increases the computational burden in terms of speed and memory allocation dramatically. This study revisits a rapid Bayesian approach (fastbayes). As a novel contribution, a measure of evidence is derived to select markers with effect significantly different from zero. It is based on the credibility of the highest posterior density interval next to zero in a marginalized manner. This methodology is applied to simulated data resembling a dairy cattle population in order to verify the sensitivity of testing for a given range of type-I error levels. A real data application complements this study. Sensitivity and specificity of fastbayes were similar to a variational Bayesian method, and a further reduction of computing time could be achieved. More than 50% of the simulated causative variants were identified. The most complex model containing different kinds of genetic effects and their pairwise interactions yielded the best outcome over a range of type-I error levels. The validation study showed that fastbayes is a dual-purpose tool for genomic inferences - it is applicable to predict future outcome of not-yet phenotyped individuals with high precision as well as to estimate and test single-marker effects. Furthermore, it allows the estimation of billions of interaction effects.

SUBMITTER: Wittenburg D

PROVIDER: S-EPMC6282823 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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An approximate Bayesian significance test for genomic evaluations.

Wittenburg Dörte D Liebscher Volkmar V

Biometrical journal. Biometrische Zeitschrift 20180812 6

Genomic information can be used to study the genetic architecture of some trait. Not only the size of the genetic effect captured by molecular markers and their position on the genome but also the mode of inheritance, which might be additive or dominant, and the presence of interactions are interesting parameters. When searching for interacting loci, estimating the effect size and determining the significant marker pairs increases the computational burden in terms of speed and memory allocation ...[more]

PMID: 30101421

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Project description:BackgroundThe Approximate Bayesian Computation (ABC) approach has been used to infer demographic parameters for numerous species, including humans. However, most applications of ABC still use limited amounts of data, from a small number of loci, compared to the large amount of genome-wide population-genetic data which have become available in the last few years.ResultsWe evaluated the performance of the ABC approach for three 'population divergence' models - similar to the 'isolation with migration' model - when the data consists of several hundred thousand SNPs typed for multiple individuals by simulating data from known demographic models. The ABC approach was used to infer demographic parameters of interest and we compared the inferred values to the true parameter values that was used to generate hypothetical "observed" data. For all three case models, the ABC approach inferred most demographic parameters quite well with narrow credible intervals, for example, population divergence times and past population sizes, but some parameters were more difficult to infer, such as population sizes at present and migration rates. We compared the ability of different summary statistics to infer demographic parameters, including haplotype and LD based statistics, and found that the accuracy of the parameter estimates can be improved by combining summary statistics that capture different parts of information in the data. Furthermore, our results suggest that poor choices of prior distributions can in some circumstances be detected using ABC. Finally, increasing the amount of data beyond some hundred loci will substantially improve the accuracy of many parameter estimates using ABC.ConclusionsWe conclude that the ABC approach can accommodate realistic genome-wide population genetic data, which may be difficult to analyze with full likelihood approaches, and that the ABC can provide accurate and precise inference of demographic parameters from these data, suggesting that the ABC approach will be a useful tool for analyzing large genome-wide datasets.

Dataset Information

An approximate Bayesian significance test for genomic evaluations.

Publications

An approximate Bayesian significance test for genomic evaluations.

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