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Testing allele homogeneity: the problem of nested hypotheses

Authors :
Eduardo Yoshio Nakano
Carlos Eduardo Pereira
Rafael Izbicki
Ana Gabriela Hounie
Victor Fossaluza
Source :
BMC Genetics, Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, BMC Genetics, Vol 13, Iss 1, p 103 (2012), Repositório Institucional da UnB, Universidade de Brasília (UnB), instacron:UNB
Publication Year :
2012
Publisher :
BioMed Central, 2012.

Abstract

Background The evaluation of associations between genotypes and diseases in a case-control framework plays an important role in genetic epidemiology. This paper focuses on the evaluation of the homogeneity of both genotypic and allelic frequencies. The traditional test that is used to check allelic homogeneity is known to be valid only under Hardy-Weinberg equilibrium, a property that may not hold in practice. Results We first describe the flaws of the traditional (chi-squared) tests for both allelic and genotypic homogeneity. Besides the known problem of the allelic procedure, we show that whenever these tests are used, an incoherence may arise: sometimes the genotypic homogeneity hypothesis is not rejected, but the allelic hypothesis is. As we argue, this is logically impossible. Some methods that were recently proposed implicitly rely on the idea that this does not happen. In an attempt to correct this incoherence, we describe an alternative frequentist approach that is appropriate even when Hardy-Weinberg equilibrium does not hold. It is then shown that the problem remains and is intrinsic of frequentist procedures. Finally, we introduce the Full Bayesian Significance Test to test both hypotheses and prove that the incoherence cannot happen with these new tests. To illustrate this, all five tests are applied to real and simulated datasets. Using the celebrated power analysis, we show that the Bayesian method is comparable to the frequentist one and has the advantage of being coherent. Conclusions Contrary to more traditional approaches, the Full Bayesian Significance Test for association studies provides a simple, coherent and powerful tool for detecting associations.

Details

Language :
English
ISSN :
14712156
Volume :
13
Database :
OpenAIRE
Journal :
BMC Genetics
Accession number :
edsair.doi.dedup.....001345dc4fa189eaa9724454bb17ccef