Genotype-based Case-Control Analysis, Violation of Hardy-Weinberg Equilibrium, and Phase Diagrams

Details Genotype-based Case-Control Analysis, Violation of Hardy-Weinberg Equilibrium, and Phase Diagrams Genotype-based Case-Control Analysis, Violation of Hardy-Weinberg Equilibrium, and Phase Diagrams

2006-11-28

arxiv.org/abs/q-bio/0611092v2

Proceedings of the 5th Asia-Pacific Bioinformatics Conference, eds. David Shankoff, Lusheng Wang, Francis Chin, pp.185-194 (Im

Biology

Quantitative Biology

Quantitative Methods

10 pages, 2 figures

Scientific paper

We study in detail a particular statistical method in genetic case-control analysis, labeled "genotype-based association", in which the two test results from assuming dominant and recessive model are combined in one optimal output. This method differs both from the allele-based association which artificially doubles the sample size, and the direct chi-square test on 3-by-2 contingency table which may overestimate the degree of freedom. We conclude that the comparative advantage (or disadvantage) of the genotype-based test over the allele-based test mainly depends on two parameters, the allele frequency difference delta and the Hardy-Weinberg disequilibrium coefficient difference delta_epsilon. Six different situations, called "phases", characterized by the two X^2 test statistics in allele-based and genotype-based test, are well separated in the phase diagram parameterized by delta and delta_epsilon. For two major groups of phases, a single parameter theta = tan^-1 (delta/delta_epsilon) is able to achieves an almost perfect phase separation. We also applied the analytic result to several types of disease models. It is shown that for dominant and additive models, genotype-based tests are favored over allele-based tests.

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