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Comparison of two‐phase analyses for case–control genetic association studies
Author(s) -
Zheng Gang,
Meyer Mark,
Li Wentian,
Yang Yaning
Publication year - 2008
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.3336
Subject(s) - statistics , statistic , test statistic , association (psychology) , genetic association , phase (matter) , test (biology) , mathematics , econometrics , statistical hypothesis testing , computer science , genetics , biology , genotype , psychology , paleontology , chemistry , organic chemistry , single nucleotide polymorphism , psychotherapist , gene
Abstract To test for genetic association between a marker and a complex disease using a case–control design, Cochran–Armitage trend tests (CATTs) and Pearson's chi‐square test are often employed. Both tests are genotype‐based. Song and Elston ( Statist. Med. 2006; 25 :105–126) introduced the Hardy–Weinberg disequilibrium trend test and combined it with CATT to test for association. Compared to using a single statistic to test for case–control genetic association (referred to as single‐phase analysis), two‐phase analysis is a new strategy in that it employs two test statistics in one analysis framework, each statistic using all available case–control data. Two such two‐phase analysis procedures were studied, in which Hardy–Weinberg equilibrium (HWE) in the population is a key assumption, although the procedures are robust to moderate departure from HWE. Our goal in this article is to study a new two‐phase procedure and compare all three two‐phase analyses and common single‐phase procedures by extensive simulation studies. For illustration, the results are applied to real data from two case–control studies. On the basis of the results, we conclude that with an appropriate choice of significance level for the analysis in phase 1, some two‐phase analyses could be more powerful than commonly used test statistics. Copyright © 2008 John Wiley & Sons, Ltd.