The power of generalized odds ratio in assessing association in genetic studies with known mode of inheritance

Abstract

The generalized odds ratio (OR_G) is a novel model-free approach to test the association in genetic studies by estimating the overall risk effect based on the complete genotype distribution. However, the power of OR_G has not been explored and, particularly, in a setting where the mode of inheritance is known. A population genetics model was simulated in order to define the mode of inheritance of a pertinent gene–disease association in advance. Then, the power of OR_G was explored based on this model and compared with the chi-square test for trend. The model considered bi- and tri-allelic gene–disease associations, and deviations from the Hardy–Weinberg equilibrium (HWE). The simulations showed that bi- and tri-allelic variants have the same pattern of power results. The power of OR_G increases with increase in the frequency of mutant allele and the coefficient of selection and, of course, the degree of dominance of the mutant allele. The deviation from HWE has a considerable impact on power only for small values of the above parameters. The OR_G showed superiority in power compared with the chi-square test for trend when there is deviation from HWE; otherwise, the pattern of results was similar in both the approaches.

Keywords:

• generalized odds ratio
• power
• degree of dominance
• genetic association study
• mode of inheritance

Acknowledgements

I thank Professor Mauro Santos, Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, for useful comments and discussion.