Premium
Hidden linkage: a comparison of the affected sib pair (ASP) test and transmission/disequilibrium test (TDT)
Author(s) -
McGINNIS R. E.
Publication year - 1998
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1046/j.1469-1809.1998.6220159.x
Subject(s) - linkage disequilibrium , locus (genetics) , transmission disequilibrium test , allele , genetics , statistic , pedigree chart , identity by descent , biology , statistics , mathematics , haplotype , gene
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 χ 2 statistic (χ 2 tdt ), and a second for identity‐by‐descent (ibd) marker allele ‘sharing’ ( P s ) which determines the magnitude of the ASP test statistic (χ 2 asp ). I also consider the ASP test applied to a completely polymorphic marker and demonstrate that the probability of ASP marker allele sharing ( P s ) is identical to P s 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 P t , P s 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).