Methodological Issues

How to Model a Complex Trait
2. Analysis with Two Disease Loci
Konstantin Strauch, Rolf Fimmers, Max P. Baur, Thomas F. Wienker

Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany

Address of Corresponding Author

Hum Hered 2003;56:200-211 (DOI: 10.1159/000076394)

  Key Words

• Linkage analysis
• Complex traits
• Locus heterogeneity
• Genotype-phenotype relation
• Two-locus models
• Epistasis
• Interaction

  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.

Copyright © 2003 S. Karger AG, Basel

  Author Contacts

Dr. Konstantin Strauch
Institute for Medical Biometry, Informatics, and Epidemiology
University of Bonn, Sigmund-Freud-Str. 25
DE-53105 Bonn (Germany)
Tel. +49 228 287 4812, Fax +49 228 287 5854, E-Mail strauch@uni-bonn.de

  Article Information

Received: October 31, 2002
Accepted after revision: July 1, 2003
Number of Print Pages : 12
Number of Figures : 1, Number of Tables : 4, Number of References : 43