Trend Tests for Case-Control Studies of Genetic Markers: Power, Sample Size and RobustnessFreidlin B. · Zheng G. · Li Z. · Gastwirth J.L.
aBiometric Research Branch and bBiostatistics Branch, National Cancer Institute, Rockville, Md., cOffice of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, Md., dBiostatistics Center, George Washington University, Rockville, Md., and eDepartment of Statistics, George Washington University, Washington, D.C., USA
The Cochran-Armitage trend test is commonly used as a genotype-based test for candidate gene association. Corresponding to each underlying genetic model there is a particular set of scores assigned to the genotypes that maximizes its power. When the variance of the test statistic is known, the formulas for approximate power and associated sample size are readily obtained. In practice, however, the variance of the test statistic needs to be estimated. We present formulas for the required sample size to achieve a prespecified power that account for the need to estimate the variance of the test statistic. When the underlying genetic model is unknown one can incur a substantial loss of power when a test suitable for one mode of inheritance is used where another mode is the true one. Thus, tests having good power properties relative to the optimal tests for each model are useful. These tests are called efficiency robust and we study two of them: the maximin efficiency robust test is a linear combination of the standardized optimal tests that has high efficiency and the MAX test, the maximum of the standardized optimal tests. Simulation results of the robustness of these two tests indicate that the more computationally involved MAX test is preferable.
Biometric Research Branch
National Cancer Institute
MSC 7434, Bethesda, MD 20892 (USA)
Received: January 31, 2002
Accepted: March 28, 2002
Revision received: March 22, 2002
Published online: June 11, 2009
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 8, Number of References : 13
Human Heredity (International Journal of Human and Medical Genetics)
Founded 1950 as Acta Genetica et Statistica Medica by Gunnar Dahlberg; Continued by M. Hauge (1965–1983)
Vol. 53, No. 3, Year 2002 (Cover Date: Released July 2002)
Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (Print), eISSN: 1423–0062 (Online)
For additional information: http://www.karger.ch/journals/hhe