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Randomization tests of disease-marker associations

Published online by Cambridge University Press:  01 January 1997

A. P. MORRIS ,
R. N. CURNOW  and
J. C. WHITTAKER
A. P. MORRIS
Affiliation:
University of Reading, Department of Applied Statistics, Harry Pitt Building, Whiteknights Road, PO Box 240, Reading RG6 2FN, U.K.
R. N. CURNOW
Affiliation:
University of Reading, Department of Applied Statistics, Harry Pitt Building, Whiteknights Road, PO Box 240, Reading RG6 2FN, U.K.
J. C. WHITTAKER
Affiliation:
University of Reading, Department of Applied Statistics, Harry Pitt Building, Whiteknights Road, PO Box 240, Reading RG6 2FN, U.K.
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Abstract

A powerful test for population association of a disease with alleles at a bi-allelic marker locus is the transmission/disequilibrium test (TDT). A generalization of the test to multi-allelic marker locus is proposed which utilizes the maximal association of individual alleles with the disease, given by the maximum TDT statistic, TDT(max). To overcome the multiple testing problem encountered when using the maximal association to test the null hypothesis of no disease-marker association, a randomization procedure is developed. An investigation of the power of the test suggests that the randomization procedure performs almost as well as a recently proposed likelihood based test of linkage disequilibrium. The advantage of the new test is that it can be applied sequentially, based on a one-sided version of the TDT statistic, for investigating patterns of association of several individual alleles with the disease.

Type
Research Article
Information
Annals of Human Genetics , Volume 61 , Issue 1 , January 1997 , pp. 47 - 58
Copyright
University College London 1997

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