title: Power comparison of Cochran-Armitage trend test against allelic and genotypic tests in large-scale case-control genetic association studies.
abstract: The Cochran-Armitage trend test (CA) has become a standard procedure for association testing in large-scale genome-wide association studies (GWAS). However, when the disease model is unknown, there is no consensus on the most powerful test to be used between CA, allelic, and genotypic tests. In this article, we tackle the question of whether CA is best suited to single-locus scanning in GWAS and propose a power comparison of CA against allelic and genotypic tests. Our approach relies on the evaluation of the Taylor decompositions of non-centrality parameters, thus allowing an analytical comparison of the power functions of the tests. Compared to simulation-based comparison, our approach offers the advantage of simultaneously accounting for the multidimensionality of the set of features involved in power functions. Although power for CA depends on the sample size, the case-to-control ratio and the minor allelic frequency (MAF), our results first show that it is largely influenced by the mode of inheritance and a deviation from Hardy-Weinberg Equilibrium (HWE). Furthermore, when compared to other tests, CA is shown to be the most powerful test under a multiplicative disease model or when the single-nucleotide polymorphism largely deviates from HWE. In all other situations, CA lacks in power and differences can be substantial, especially for the recessive mode of inheritance. Finally, our results are illustrated by the comparison of the performances of the statistics in two genome scans.
authors.affiliation: Agrocampus Ouest, UMR 6625, IRMAR, Rennes, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Emily
mesh_terms: D000465:Algorithms; D000483:Alleles; D035843:Biomedical Research / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models
keywords: Cochran-Armitage trend test; Hardy–Weinberg equilibrium; Pearson’s chi-squared test; likelihood-ratio test; non-central chi-squared distribution