McGinnis R E
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104-6145, USA.
Ann Hum Genet. 1998 Mar;62(Pt 2):159-79. doi: 10.1046/j.1469-1809.1998.6220159.x.
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).
在描述双等位基因疾病位点的一般代数模型下，我比较了传递/不平衡检验（TDT）和患病同胞对检验（ASP）。假设与双等位基因标记存在连锁关系，我推导出两个二项式概率，一个用于确定TDT卡方统计量（χ²tdt）大小的亲代等位基因“传递”（Pt），另一个用于确定ASP检验统计量（χ²asp）大小的基于血缘一致性（ibd）的标记等位基因“共享”（Ps）。我还考虑了应用于完全多态性标记的ASP检验，并证明ASP标记等位基因共享（Ps）的概率与在与疾病位点处于平衡状态的双等位基因标记中观察到的Ps相同。我基于Pt、Ps以及在标记处具有信息性的确定父母的比例（H/F）的表达式，提出了一个用于确定TDT和ASP检验功效的一般框架。先前基于Ott（1989年）以及Risch和Merikangas（1996年）工作的两项关于TDT功效的分析研究被证明是这个一般框架的特殊情况。此外，我展示了我提出的框架与基于Sham和Curtis（1995年）工作的针对多等位基因标记的TDT功效的第三次分析研究之间的关系。
