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How to model a complex trait. 2. Analysis with two disease loci.

Konstantin Strauch·Rolf Fimmers·Max P Baur·Thomas F Wienker
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Abstract

Complex traits are often governed by more than one trait locus. The first step towards an adequate model for such diseases is a linkage analysis with two trait loci. Such an analysis can be expected to have higher power to detect linkage than a standard single-trait-locus linkage analysis. However, it is crucial to accurately specify the parameters of the two-locus model. Here, we recapitulate the general two-locus model with and without genomic imprinting. We relate heterogeneity, multiplicative, and additive two-locus models to biological or pathophysiological mechanisms, and give the corresponding averaged ("best-fitting") single-trait-locus models for each of the two loci. Furthermore, we derive the two-locus penetrances from the averaged single-locus models, under the assumption of one of the three model classes mentioned above. Using these formulae, if the best-fitting single-locus models are available, investigators may perform a two-trait-locus linkage analysis under a realistic model. This procedure will maximize the power to detect linkage for traits which are governed by two or more loci, and lead to more accurate estimates of the disease-locus positions.

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Computer SimulationGenetic Diseases, InbornGenetic HeterogeneityGenetic LinkageHumansLod ScoreModels, GeneticModels, StatisticalQuantitative Trait LociJournal ArticleResearch Support, Non-U.S. Gov't

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Konstantin Strauch, Rolf Fimmers, Max P Baur, Thomas F Wienker. 2003. How to model a complex trait. 2. Analysis with two disease loci.. https://doi.org/10.1159/000076394

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