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Abstract: In case–control genetic association studies, a standard practice is to perform the Cochran‐Armitage (CA) trend test under the assumption of the additive model because of its robustness. We could even identify situations in which it outperformed the analysis model consistent with the underlying inheritance mode. In this article, we analytically reveal the statistical basis that leads to the phenomenon. By elucidating the origin of the CA trend test as a linear regression model, we decompose Pearson's χ2‐test statistic into two components—one is the CA trend test statistic that measures the goodness of fit of the linear regression model, and the other measures the discrepancy between data and the linear regression model. Under this framework, we show that the additive coding scheme, as well as the multiplicative coding scheme, increases the coefficient of determination of the regression model by increasing the spread of data points. We also obtain the conditions under which the CA trend test statistic equals the MAX statistic and Pearson's χ2‐test statistic. [ABSTRACT FROM AUTHOR]

In genetic case-control association studies, a standard practice is to perform the Cochran-Armitage (CA) trend test with 1 degree-of-freedom (d.f.) under the assumption of an additive model. However, when the true genetic model is recessive or near recessive, it is outperformed by Pearson's χ2 test with 2 d.f. In this article, we analytically reveal the statistical basis that leads to the phenomenon. First, we show that the CA trend test examines the location shift between the case and control groups, whereas Pearson's χ2 test examines both the location and dispersion shifts between the two groups. Second, we show that under the additive model, the effect of location deviation outweighs that of the dispersion deviation and vice versa under a near recessive model. Therefore, Pearson's χ2 test is a more robust test than the CA trend test, and it outperforms the latter when the mode of inheritance evolves to the recessive end. [ABSTRACT FROM AUTHOR]

In genetic case-control association studies, a standard practice is to perform the Cochran-Armitage (CA) trend test with 1 degree-of-freedom (d.f.) under the assumption of an additive model. However, when the true genetic model is recessive or near recessive, it is outperformed by Pearson's χ 2 test with 2 d.f. In this article, we analytically reveal the statistical basis that leads to the phenomenon. First, we show that the CA trend test examines the location shift between the case and control groups, whereas Pearson's χ 2 test examines both the location and dispersion shifts between the two groups. Second, we show that under the additive model, the effect of location deviation outweighs that of the dispersion deviation and vice versa under a near recessive model. Therefore, Pearson's χ 2 test is a more robust test than the CA trend test, and it outperforms the latter when the mode of inheritance evolves to the recessive end., (© 2017 John Wiley & Sons Ltd/University College London.)