Hidden linkage: a comparison of the affected sib pair (ASP) test and transmission/disequilibrium test (TDT).
I compare the transmission/disequilibrium test (TDT) and affected sib pair (ASP) test under a general algebraic model describing a bi-allelic disease locus. Assuming linkage to a bi-allelic marker, I derive two binomial probabilities, one for parental allele 'transmission' (Pt) which determines the magnitude of the TDT chi 2 statistic (chi 2tdt), and a second for identity-by-descent (ibd) marker allele 'sharing' (Ps) which determines the magnitude of the ASP test statistic (chi 2asp). I also consider the ASP test applied to a completely polymorphic marker and demonstrate that the probability of ASP marker allele sharing (Ps) is identical to Ps observed for a bi-allelic marker in equilibrium with the disease locus. I present a general framework for determining the power of the TDT and ASP test based on expressions for Pt, Ps and the proportion (H/F) of ascertained parents who are informative at the marker. Two previous analytic investigations of TDT power based on the work of Ott (1989), and Risch & Merikangas (1996) are shown to be special cases of this general framework. In addition, I show the relationship between the framework I present and a third analytic investigation of TDT power for multi-allelic markers based on the work of Sham & Curtis (1995).
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145, USA.
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McGinnis
D030342:Genetic Diseases, Inborn / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D009679:Nuclear Family