Markus Neuhäuser1. 1. Department of Mathematics and Statistics, University of Otago, Dunedin, New Zealand. mneuhauser@maths.otago.ac.nz
Abstract
OBJECTIVES: The association of a candidate gene with disease can be evaluated by a case-control study in which the genotype distribution is compared for diseased cases and unaffected controls. Usually, the data are analyzed with Armitage's test using the asymptotic null distribution of the test statistic. Since this test does not generally guarantee a type I error rate less than or equal to the significance level alpha, tests based on exact null distributions have been investigated. METHODS: An algorithm to generate the exact null distribution for both Armitage's test statistic and a recently proposed modification of the Baumgartner-Weiss-Schindler statistic is presented. I have compared the tests in a simulation study. RESULTS: The asymptotic Armitage test is slightly anticonservative whereas the exact tests control the type I error rate. The exact Armitage test is very conservative, but the exact test based on the modification of the Baumgartner-Weiss-Schindler statistic has a type I error rate close to alpha. The exact Armitage test is the least powerful test; the difference in power between the other two tests is often small and the comparison does not show a clear winner. CONCLUSION: Simulation results indicate that an exact test based on the modification of the Baumgartner-Weiss-Schindler statistic is preferable for the analysis of case-control studies of genetic markers. Copyright 2002 S. Karger AG, Basel
OBJECTIVES: The association of a candidate gene with disease can be evaluated by a case-control study in which the genotype distribution is compared for diseased cases and unaffected controls. Usually, the data are analyzed with Armitage's test using the asymptotic null distribution of the test statistic. Since this test does not generally guarantee a type I error rate less than or equal to the significance level alpha, tests based on exact null distributions have been investigated. METHODS: An algorithm to generate the exact null distribution for both Armitage's test statistic and a recently proposed modification of the Baumgartner-Weiss-Schindler statistic is presented. I have compared the tests in a simulation study. RESULTS: The asymptotic Armitage test is slightly anticonservative whereas the exact tests control the type I error rate. The exact Armitage test is very conservative, but the exact test based on the modification of the Baumgartner-Weiss-Schindler statistic has a type I error rate close to alpha. The exact Armitage test is the least powerful test; the difference in power between the other two tests is often small and the comparison does not show a clear winner. CONCLUSION: Simulation results indicate that an exact test based on the modification of the Baumgartner-Weiss-Schindler statistic is preferable for the analysis of case-control studies of genetic markers. Copyright 2002 S. Karger AG, Basel
Authors: Albert Rosenberger; Thomas Illig; Katrin Korb; Norman Klopp; Vera Zietemann; Gabi Wölke; Eckart Meese; Gerhard Sybrecht; Florian Kronenberg; Matthias Cebulla; Maria Degen; Peter Drings; Andreas Gröschel; Nikolaus Konietzko; Karsten Grosse Kreymborg; Karl Häussinger; Gerd Höffken; Bettina Jilge; You-Dschun Ko; Harald Morr; Christine Schmidt; E-Wilhelm Schmidt; Dagmar Täuscher; Heike Bickeböller; H-Erich Wichmann Journal: BMC Cancer Date: 2008-02-25 Impact factor: 4.430