title: Exact tests for the analysis of case-control studies of genetic markers.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Mathematics and Statistics, University of Otago, Dunedin, New Zealand. mneuhauser@maths.otago.ac.nz
authors.forename: Markus
authors.initials: M
authors.lastname: Neuhäuser
mesh_terms: D000465:Algorithms; D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D005819:Genetic Markers; D012107:Research Design; D015983:Selection Bias
chemical_list: D005819:Genetic Markers