A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test - PubMed (original) (raw)
A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test
R S Spielman et al. Am J Hum Genet. 1998 Feb.
Abstract
Linkage analysis with genetic markers has been successful in the localization of genes for many monogenic human diseases. In studies of complex diseases, however, tests that rely on linkage disequilibrium (the simultaneous presence of linkage and association) are often more powerful than those that rely on linkage alone. This advantage is illustrated by the transmission/disequilibrium test (TDT). The TDT requires data (marker genotypes) for affected individuals and their parents; for some diseases, however, data from parents may be difficult or impossible to obtain. In this article, we describe a method, called the "sib TDT" (or "S-TDT"), that overcomes this problem by use of marker data from unaffected sibs instead of from parents, thus allowing application of the principle of the TDT to sibships without parental data. In a single collection of families, there might be some that can be analyzed only by the TDT and others that are suitable for analysis by the S-TDT. We show how all the data may be used jointly in one overall TDT-type procedure that tests for linkage in the presence of association. These extensions of the TDT will be valuable for the study of diseases of late onset, such as non-insulin-dependent diabetes, cardiovascular diseases, and other diseases associated with aging.
Comment in
- The sib transmission/disequilibrium test is a Mantel-Haenszel test.
Laird NM, Blacker D, Wilcox M. Laird NM, et al. Am J Hum Genet. 1998 Dec;63(6):1915-6. doi: 10.1086/302151. Am J Hum Genet. 1998. PMID: 9838272 Free PMC article. No abstract available. - Using exact P values to compare the power between the reconstruction-combined transmission/disequilibrium test and the sib transmission/disequilibrium test.
Knapp M. Knapp M. Am J Hum Genet. 1999 Oct;65(4):1208-10. doi: 10.1086/302591. Am J Hum Genet. 1999. PMID: 10486344 Free PMC article. No abstract available.
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