Abstract
The transmission/disequilibrium (TD) test (TDT), proposed, by Spielman et al., for binary traits is a powerful method for detection of linkage between a marker locus and a disease locus, in the presence of allelic association. As a test for linkage disequilibrium, the TDT makes the assumption that any allelic association present is due to linkage. Allison proposed a series of TD-type tests for quantitative traits and calculated their power, assuming that the marker locus is the disease locus. All these tests assume that the observations are independent, and therefore they are applicable, as a test for linkage, only for nuclear-family data. In this report, we propose a regression-based TD-type test for linkage between a marker locus and a quantitative trait locus, using information on the parent-to-offspring transmission status of the associated allele at the marker locus. This method does not require independence of observations, thus allowing for analysis of pedigree data as well, and allows adjustment for covariates. We investigate the statistical power and validity of the test by simulating markers at various recombination fractions from the disease locus.
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Selected References
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- Allison D. B. Transmission-disequilibrium tests for quantitative traits. Am J Hum Genet. 1997 Mar;60(3):676–690. [PMC free article] [PubMed] [Google Scholar]
- Cleves M. A., Olson J. M., Jacobs K. B. Exact transmission-disequilibrium tests with multiallelic markers. Genet Epidemiol. 1997;14(4):337–347. doi: 10.1002/(SICI)1098-2272(1997)14:4<337::AID-GEPI1>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
- Elston R. C., George V. T., Severtson F. The Elston-Stewart algorithm for continuous genotypes and environmental factors. Hum Hered. 1992;42(1):16–27. doi: 10.1159/000154043. [DOI] [PubMed] [Google Scholar]
- Elston R. C., Stewart J. A general model for the genetic analysis of pedigree data. Hum Hered. 1971;21(6):523–542. doi: 10.1159/000152448. [DOI] [PubMed] [Google Scholar]
- George V. T., Elston R. C. Testing the association between polymorphic markers and quantitative traits in pedigrees. Genet Epidemiol. 1987;4(3):193–201. doi: 10.1002/gepi.1370040304. [DOI] [PubMed] [Google Scholar]
- Haseman J. K., Elston R. C. The investigation of linkage between a quantitative trait and a marker locus. Behav Genet. 1972 Mar;2(1):3–19. doi: 10.1007/BF01066731. [DOI] [PubMed] [Google Scholar]
- Risch N. J., Zhang H. Mapping quantitative trait loci with extreme discordant sib pairs: sampling considerations. Am J Hum Genet. 1996 Apr;58(4):836–843. [PMC free article] [PubMed] [Google Scholar]
- Spielman R. S., Ewens W. J. The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet. 1996 Nov;59(5):983–989. [PMC free article] [PubMed] [Google Scholar]
- Spielman R. S., McGinnis R. E., Ewens W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993 Mar;52(3):506–516. [PMC free article] [PubMed] [Google Scholar]