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Should ambiguous trios for the TDT be discarded?

Published online by Cambridge University Press:  20 February 2001

P. C. SHAM
Affiliation:
Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK
J. H. ZHAO
Affiliation:
Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK
I. WALDMAN
Affiliation:
Department of Psychology, Emory University, 532 N. Kilgo Circle, Atlanta, GA 30322, USA
D. CURTIS
Affiliation:
Academic Department of Psychological Medicine, St Bartholomew's and Royal London School of Medicine and Dentistry, 3rd Floor Alexandra Wing, Royal London Hospital, Whitechapel, London E1 1BB, UK
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Abstract

It is well known that the TDT proposed by Spielman et al. (1993) is potentially anti-conservative if families with one missing parental genotype are included (Curtis & Sham, 1995). We now bring attention to another situation that could give rise to an inflated rate of false positive results. This occurs when families in which the affected offspring and both parents have the same heterozygous genotype are excluded. If the heterozygous genotype is denoted as AB, then it is clear that one parent must have transmitted allele A and the other allele B. The standard TDT procedure is to increment the counts for transmissions of both A and B by one. It may seem reasonable to disregard such trios because it is ambiguous which parent has transmitted which allele. Although the resulting test statistic would retain all the information concerning preferential transmission of alleles, it can be shown that referring it to a χ2 distribution would lead to an increased type I error rate (see Appendix A).

Type
SHORT COMMUNICATION
Copyright
University College London 2000

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