Comparison of statistical power between 2x2 allele frequency and allele positivity tables in case-control studies of complex disease genes

Citation
J. Ohashi et al., Comparison of statistical power between 2x2 allele frequency and allele positivity tables in case-control studies of complex disease genes, ANN HUM GEN, 65, 2001, pp. 197-206
Citations number
11
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
ANNALS OF HUMAN GENETICS
ISSN journal
0003-4800 → ACNP
Volume
65
Year of publication
2001
Part
2
Pages
197 - 206
Database
ISI
SICI code
0003-4800(200103)65:<197:COSPB2>2.0.ZU;2-N
Abstract
In case-control studies of complex disease genes, allele frequencies or all ele positivities at candidate loci or markers are compared between case and controls. Although 2 x 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 chi (2) test), little is known a bout the difference in power between the two tables. In this study, we inve stigated the number of subjects required in power of 1 - beta with a signif icance level of alpha for the allele frequency and allele positivity tables . A large difference in the required number of subjects was found between t he 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 showing for the identifi cation of susceptibility allele showing a recessive MOI or a multiplicative MOI. In the case of an additive MOI, a suitable table was determined by co mbining the frequency of the susceptibility allele and the penetrance. Thes e 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 simu lation analysis revealed that the type I error rate was not much inflated u nder the null hypothesis of no association, even when a statistical test wa s performed twice using both allele frequency and allele positivity tables. In contrast, under the alternative hypothesis, the loss of power was marke d when a test was performed using both tables, without adjustment of multip licity, in case-control studies of complex disease genes when the study obj ective is exploratory.