Heredity

DOI: 10.1038/s41437-019-0232-0

Date of publication: 2019-05-29

Abstract:

Standard statistical tests for Hardy-Weinberg equilibrium assume the equality of allele frequencies in the sexes, whereas tests for the equality of allele frequencies in the sexes assume Hardy–Weinberg equilibrium. This produces a circularity in the testing of genetic variants, which has recently been resolved with new frequentist likelihood and exact procedures. In this paper, we tackle the same problem by posing it as a Bayesian model comparison problem. We formulate an exhaustive set of ten alternative scenarios for biallelic genetic variants. Using Dirichlet and Beta priors for genotype and allele frequencies, we derive marginal likelihoods for all scenarios, and select the most likely scenario using the posterior probabilities that each of these scenarios is the one in place. Different from the usual frequentist testing approach, the Bayesian approach allows one to compare any number of models, and not just two at a time, and the models compared do not have to be nested. We illustrate our Bayesian approach with genetic data from the 1,000 genomes project and through a simulation study.]]>

Heredity

num. 119, p. 226-236

DOI: 10.1038/hdy.2017.30

Date of publication: 2017-07

Abstract:

The X chromosome is a relatively large chromosome, harboring a lot of genetic information. Much of the statistical analysis of X-chromosomal information is complicated by the fact that males only have one copy. Recently, frequentist statistical tests for Hardy–Weinberg equilibrium have been proposed specifically for dealing with markers on the X chromosome. Bayesian test procedures for Hardy–Weinberg equilibrium for the autosomes have been described, but Bayesian work on the X chromosome in this context is lacking. This paper gives the first Bayesian approach for testing Hardy–Weinberg equilibrium with biallelic markers at the X chromosome. Marginal and joint posterior distributions for the inbreeding coefficient in females and the male to female allele frequency ratio are computed, and used for statistical inference. The paper gives a detailed account of the proposed Bayesian test, and illustrates it with data from the 1000 Genomes project. In that implementation, a novel approach to tackle multiple testing from a Bayesian perspective through posterior predictive checks is used.]]>