On estimation of the variance in Cochran-Armitage trend tests for genetic association using case-control studies.

Abstract:

:The Cochran-Armitage trend test has been used in case-control studies for testing genetic association. As the variance of the test statistic is a function of unknown parameters, e.g. disease prevalence and allele frequency, it must be estimated. The usual estimator combining data for cases and controls assumes they follow the same distribution under the null hypothesis. Under the alternative hypothesis, however, the cases and controls follow different distributions. Thus, the power of the trend tests may be affected by the variance estimator used. In particular, the usual method combining both cases and controls is not an asymptotically unbiased estimator of the null variance when the alternative is true. Two different estimates of the null variance are available which are consistent under both the null and alternative hypotheses. In this paper, we examine sample size and small sample power performance of trend tests, which are optimal for three common genetic models as well as a robust trend test based on the three estimates of the variance and provide guidelines for choosing an appropriate test.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Zheng G,Gastwirth JL

doi

10.1002/sim.2250

subject

Has Abstract

pub_date

2006-09-30 00:00:00

pages

3150-9

issue

18

eissn

0277-6715

issn

1097-0258

journal_volume

25

pub_type

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