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A logistic regression based extension of the TDT for continuous and categorical traits

Published online by Cambridge University Press:  01 July 1999

I. D. WALDMAN
Affiliation:
Department of Psychology, Emory University, 532 N. Kilgo Circle, Atlanta, GA 30322 USA
B. F. ROBINSON
Affiliation:
Department of Psychology, Emory University, 532 N. Kilgo Circle, Atlanta, GA 30322 USA
D. C. ROWE
Affiliation:
Division of Family Studies & Graduate Program in Genetics, Campus Box 210033, University of Arizona, Tucson, AZ 85721 USA
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Abstract

The transmission disequilibrium test (TDT), designed as a test of linkage in the presence of association (i.e. linkage disequilibrium), has received considerable attention in the recent statistical genetics literature due to its advantages over other within-family analytic methods. One limitation of the conventional TDT is its application solely to linkage disequilibrium between a genetic marker and a single categorical trait (e.g. presence or absence of a disease). In this paper, we present an extension of the TDT using logistic regression to examine the relation between a candidate gene or genetic marker and one or more continuous or categorical explanatory variables. This logistic regression extension of the TDT possesses all of the desirable features of the conventional TDT, as well as many advantages associated with traditional regression analysis. We describe the model and its properties, as well as a number of its possible applications, and apply it to examine linkage disequilibrium between the dopamine receptor D2 gene (DRD2) and symptoms of childhood attention deficit hyperactivity disorder (ADHD). We also briefly compare the logistic regression TDT to other quantitative TDTs that have been proposed in the literature, and highlight the advantages of a regression-based approach for examining the relation between a candidate gene and one or more continuous or categorical traits. Given its features, we regard the logistic regression extension of the TDT as a flexible new data analytic method with extensive potential applications to problems in medical, psychiatric, and behavioral genetics.

Type
Research Article
Copyright
© University College London 1999

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