Sample Size Requirements

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Sample Size Requirements

Michael Knapp, University of Bonn, Bonn, Germany

Published online: January 2006

DOI: 10.1038/npg.els.0005436

Full Article on Wiley Online Library

Abstract
References

Sample size requirements in the context of linkage analysis between a trait and genetic markers refer to the calculation of the sample size required for a linkage study to guarantee a certain power of the study against an assumed inheritance model. The power against an assumed inheritance model is the probability of correctly declaring a linkage when in fact the assumed inheritance model is true and the trait and marker loci are linked.

Keywords: power; inheritance model; parametric linkage analysis; affected sibling pair test; transmission/disequilibrium test

References
	Blackwelder WC and Elston RC (1985) A comparison of sib-pair linkage tests for disease susceptibility loci. Genetic Epidemiology 2: 85–97.
	book Feller W (1970) An Introduction to Probability Theory and its Applications, 3rd edn. New York, NY: Wiley.
	Knapp M (1999) A note on power approximations for the transmission/disequilibrium test. American Journal of Human Genetics 64: 1177–1185.
	Ploughman LM and Boehnke M (1989) Estimating the power of a proposed linkage study for a complex genetic trait. American Journal of Human Genetics 44: 543–551.
	Risch N (1990) Linkage strategies for genetically complex traits. II. The power of affected relative pairs. American Journal of Human Genetics 46: 229–241.
	Risch N and Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273: 1516–1517.
	book SAS Institute Inc. (1990) SAS Language: Reference, version 6, 1st edn. Cary, NC: SAS Institute.
	Spielman RS, McGinnis RE and Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). American Journal of Human Genetics 52: 502–516.
	Suarez BK, Rice J and Reich T (1978) The generalized sib pair IBD distribution: its use in the detection of linkage. Annals of Human Genetics 42: 87–94.
	Terwilliger JD, Speer M and Ott J (1993) Chromosome-based method of rapid computer simulation in human genetic linkage analysis. Genetic Epidemiology 10: 217–224.
	Weeks DE, Ott J and Lathrop GM (1990) SLINK: a general simulation program for linkage analysis. American Journal of Human Genetics 47: A204.
Further Reading
	Chen WM and Deng HW (2001) A general and accurate approach for computing the statistical power of the transmission disequilibrium test for complex disease genes. Genetic Epidemiology 21: 53–67.
	book Holmans P (2001) "Nonparametric linkage". In: Balding DJ, Bishop M and Cannings C (eds.) Handbook of Statistical Genetics, pp. 541–563. Chichester, UK: Wiley.
	Holmans P and Clayton D (1995) Efficiency of typing unaffected relatives in an affected-sib-pair linkage study with single-locus and multiple tightly linked markers. American Journal of Human Genetics 57: 1221–1232.
	Krawczak M (2001) ASP – a simulation-based power calculator for genetic linkage studies of qualitative traits, using sib-pairs. Human Genetics 109: 675–677.
	Risch N (2000) Searching for genetic determinants in the new millennium. Nature 405: 847–856.
	book Thompson EA (2001) "Linkage analysis". In: Balding DJ, Bishop M and Cannings C (eds.) Handbook of Statistical Genetics, pp. 541–563. Chichester, UK: Wiley.
	Weeks DE and Lathrop GM (1995) Polygenic disease: methods for mapping complex disease traits. Trends in Genetics 11: 513–519.
Web Links
	ePath SAS macro to compute power approximations for the TDT http://www.uni-bonn.de/~umt70e/soft.htm
	ePath SIMLINK program www.sph.umich.edu/statgen/boehnke/simlink.html
	ePath SIMULATE program ftp://linkage.rockefeller.edu/software/simulate
	ePath SLINK program ftp://linkage.rockefeller.edu/software/slink

Article Title:	Sample Size Requirements
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