Estimating the power of a proposed linkage study for a complex genetic trait

Many genetic traits have complex modes of inheritance; they may exhibit incomplete or age-dependent penetrance or fail to show any clear Mendelian inheritance pattern. As primary linkage maps for the human genome near completion, it is becoming increasingly possible to map these traits. Prior to und...

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Bibliographic Details
Published in:American journal of human genetics 1989-04, Vol.44 (4), p.543-551
Main Authors: PLOUGHMAN, L. M, BOEHNKE, M
Format: Article
Language:English
Subjects:
Biological and medical sciences
General aspects. Genetic counseling
Genetic Linkage
Genetics, Medical - methods
Genotype
Humans
Medical genetics
Medical sciences
Pedigree
Probability
Software
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Summary:Many genetic traits have complex modes of inheritance; they may exhibit incomplete or age-dependent penetrance or fail to show any clear Mendelian inheritance pattern. As primary linkage maps for the human genome near completion, it is becoming increasingly possible to map these traits. Prior to undertaking a linkage study, it is important to consider whether the pedigrees available for the proposed study are likely to provide sufficient information to demonstrate linkage, assuming a linked marker is tested. In the current paper, we describe a computer simulation method to estimate the power of a proposed study to detect linkage for a complex genetic trait, given a hypothesized genetic model for the trait. Our method simulates trait locus genotypes consistent with observed trait phenotypes, in such a way that the probability to detect linkage can be estimated by sample statistics of the maximum lod score distribution. The method uses terms available when calculating the likelihood of the trait phenotypes for the pedigree and is applicable to any trait determined by one or a few genetic loci; individual-specific environmental effects can also be dealt with. Our method provides an objective answer to the question, Will these pedigrees provide sufficient information to map this complex genetic trait?
ISSN:0002-9297
1537-6605