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Table of Contents
Vol. 48, No. 6, 1998
Issue release date: November – December
Section title: Original Paper
Hum Hered 1998;48:295–312
(DOI:10.1159/000022821)

The Power of Linkage Detection by the Transmission/Disequilibrium Tests

Xiong M.a · Guo S-W.b
a Human Genetics Center, Health Science Center, University of Texas-Houston, Houston, Tex., b Institute of Human Genetics and the Division of Epidemiology, University of Minnesota, Minneapolis, Minn., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: November 06, 1998
Issue release date: November – December

Number of Print Pages: 18
Number of Figures: 8
Number of Tables: 3

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: http://www.karger.com/HHE

Abstract

Despite growing interest in the use of transmission/disequilibrium test (TDT)-type analysis in association studies, there has been surprisingly scant attention paid to the issues as to what factors affect the power of the TDT for linkage detection. We demonstrate in this paper that the power is a function of several genetic parameters including the recombination fraction, penetrance, the age of mutant disease allele, marker allele frequency, recurrent mutation rates at marker and/or disease locus, and initial linkage disequilibrium. In general, TDT has greater power to detect linkage for a ‘recessive’-type model than for a ‘dominant’-type model. Its power also is higher when there is greater differential in marker allele frequency between disease and normal chromosomes. And since the presence of marker mutation and/or recurrent mutation at the disease locus, or the age of disease mutation, or the initial incomplete linkage disequilibrium, all hasten the process to reach linkage equilibrium, all of them can affect the power of TDT to detect linkage. The effect of marker mutation rate or the mutation rate at the disease locus can be minimal if mutation rates are low. The results on the impact of recombination fraction and of age of mutation on the power of TDT in linkage detection seem to be disheartening for gene mappers of complex diseases: for a disease with small genetic influence, a vastly large sample size is needed to detect the linkage, if the marker is not very close to the disease locus. This is particularly true if the disease is ‘old’.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: November 06, 1998
Issue release date: November – December

Number of Print Pages: 18
Number of Figures: 8
Number of Tables: 3

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: http://www.karger.com/HHE


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