The null distribution of T is the convolution of all null distributions for T i, where T i denotes the number of alleles A in family i. In essence, the test statistic of the S-TDT is the total number T of alleles A (i.e., the allele of interest) in affected children in the whole sample. To the contrary, it is easily incorporated into any computer program. It does not seem to be generally known that the calculation of exact P values for the S-TDT does not require sophisticated algorithms at all. An example of the need of small P values is the association scan proposed by Risch and Merikangas ( 1996), which requires that P values <5×10 -8 be observed in order for significance to be declared. The superiority of exact P values over asymptotic P values is evident, since it is well known (e.g., see Elston 1998) that P values obtained on the basis of theoretical large-sample approximations can be quite unreliable if they are much smaller than. As noted by Laird et al., it is possible by this identity to use commercial software such as StatXact to calculate exact P values for the S-TDT. ( 1998) pointed out that Spielman and Ewens's ( 1998) sib transmission/disequilibrium test (S-TDT) is identical to a Mantel-Haenszel test of trend. In a recent letter in the Journal, Laird et al.
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