In case-control studies of complex disease genes, allele frequencies or allele positivities at candidate
loci or markers are compared between cases and controls. Although 2 × 2 contingency tables based
on allele frequency and allele positivity are generally used to perform simple statistical tests (e.g. a
comparison of two proportions and a χ2 test), little is known about the difference in power between
the two tables. In this study, we investigated the number of subjects required to obtain a power of
1 − β with a significance level of α for the allele frequency and allele positivity tables. A large
difference in the required number of subjects was found between the two tables. Allele positivity
tables were suitable for the detection of susceptibility alleles showing a dominant mode of inheritance
(MOI). On the other hand, allele frequency tables were suitable for the identification of susceptibility
alleles showing a recessive MOI or a multiplicative MOI. In the case of an additive MOI, a suitable
table was determined by combining the frequency of the susceptibility allele and the penetrance.
These results imply that there are cases in which true association is detected based on one
contingency table and is not detected based on another. A simulation analysis revealed that the type
I error rate was not much inflated under the null hypothesis of no association, even when a statistical
test was performed twice using both allele frequency and allele positivity tables. In contrast, under
the alternative hypothesis, the loss of power was marked when a test was performed once using an
unsuitable table. In conclusion, statistical tests should be performed using both tables, without
adjustment of multiplicity, in case-control studies of complex disease genes when the study objective
is exploratory.