title: Selecting a contingency table in a population-based association study: allele frequency or positivity?
abstract: In population-based association studies, the significance of the association between a candidate gene and a disease is usually examined by a simple chi 2 test. Such studies require a 2 x 2 contingency table made up of either allele frequencies or positivities in affected and control groups. In order to investigate the influence of each 2 x 2 table on the power of the chi 2 test, P values were calculated for two penetrance models (multiplicative and additive). When the value of penetrance was small and not markedly different among genotypes, a large difference in the power of the chi 2 test was observed between the two tables. In a multiplicative model, the allele frequency table was superior to the positivity table for detecting significance. In contrast, in an additive model, the positivity table was most suitable. Selecting a contingency table was especially important for detecting true association, when the required significance level was corrected to avoid the problem of multiple hypothesis testing. The chi 2 test, therefore, should be performed for both tables to identify a susceptible gene with a low penetrance, even when no significant difference is observed in one table.
authors.affiliation: Department of Human Genetics, School of International Health, Graduate School of Medical Sciences, University of Tokyo, Japan. juno@.m.u-tokyo.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Ohashi
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000483:Alleles; D016009:Chi-Square Distribution; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical