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Lancet. 2005 Sep 17-23;366(9490):1036-44.

Genetic linkage studies.

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  • 1Mathematical Modelling and Genetic Epidemiology Division of Genomic Medicine, Henry Wellcome Laboratories for Medical Research, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK.


Linkage analysis is used to map genetic loci by use of observations of related individuals. We provide an introduction to methods commonly used to map loci that predispose to disease. Linkage analysis methods can be applied to both major gene disorders (parametric linkage) and complex diseases (model-free or non-parametric linkage). Evidence for linkage is most commonly expressed as a logarithm of the odds score. We provide a framework for interpretation of these scores and discuss the role of simulation in assessment of statistical significance and estimation of power. Genetic and phenotypic heterogeneity can also affect the success of a study, and several methods exist to address such problems.

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