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Selection Strategies for Linkage Studies Using Twins

Published online by Cambridge University Press:  21 February 2012

Hein Putter*
Affiliation:
Department of Medical Statistics, Leiden University Medical Center, University of Leiden, Leiden,The Netherlands. [email protected]
Jeremie Lebrec
Affiliation:
Department of Medical Statistics, Leiden University Medical Center, University of Leiden, Leiden,The Netherlands.
Hans C. van Houwelingen
Affiliation:
Department of Medical Statistics, Leiden University Medical Center, University of Leiden, Leiden,The Netherlands.
*
*Address for correspondence: H. Putter, Department of Medical Statistics, Leiden University Medical Center, University of Leiden, PO Box 9604, 2300 RC Leiden, The Netherlands.

Abstract

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Genetic linkage analysis for complex diseases offers a major challenge to geneticists. In these complex diseases multiple genetic loci are responsible for the disease and they may vary in the size of their contribution; the effect of any single one of them is likely to be small. In many situations, like in extensive twin registries, trait values have been recorded for a large number of individuals, and preliminary studies have revealed summary measures for those traits, like mean, variance and components of variance, including heritability. Given the small effect size, a random sample of twins will require a prohibitively large sample size. It is well known that selective sampling is far more efficient in terms of genotyping effort. In this paper we derive easy expressions for the information contributed by sib pairs for the detection of linkage to a quantitative trait locus (QTL). We consider random samples as well as samples of sib pairs selected on the basis of their trait values. These expressions can be rapidly computed and do not involve simulation. We extend our results for quantitative traits to dichotomous traits using the concept of a liability threshold model. We present tables with required sample sizes for height, insulin levels and migraine, three of the traits studied in the GenomEUtwin project.

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Articles
Copyright
Copyright © Cambridge University Press 2003