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Extension of the SIMLA Package for Generating Pedigrees with Complex Inheritance Patterns: Environmental Covariates, Gene-Gene and Gene-Environment Interaction

Author

Listed:
  • Schmidt Mike

    (Center for Human Genetics, Duke University Medical Center)

  • Hauser Elizabeth R

    (Center for Human Genetics, Duke University Medical Center)

  • Martin Eden R.

    (Center for Human Genetics, Duke University Medical Center)

  • Schmidt Silke

    (Center for Human Genetics, Duke University Medical Center)

Abstract

We have previously distributed a software package, SIMLA (SIMulation of Linkage and Association), which can be used to generate disease phenotype and marker genotype data in three-generational pedigrees of user-specified structure. To our knowledge, SIMLA is the only publicly available program that can simulate variable levels of both linkage (recombination) and linkage disequilibrium (LD) between marker and disease loci in general pedigrees. While the previous SIMLA version provided flexibility in choosing many parameters relevant for linkage and association mapping of complex human diseases, it did not allow for the segregation of more than one disease locus in a given pedigree and did not incorporate environmental covariates possibly interacting with disease susceptibility genes.Here, we present an extension of the simulation algorithm characterized by a much more general penetrance function, which allows for the joint action of up to two genes and up to two environmental covariates in the simulated pedigrees, with all possible multiplicative interaction effects between them. This makes the program even more useful for comparing the performance of different linkage and association analysis methods applied to complex human phenotypes. SIMLA can assist investigators in planning and designing a variety of linkage and association studies, and can help interpret results of real data analyses by comparing them to results obtained under a user-controlled data generation mechanism.A free download of the SIMLA package is available at http://wwwchg.duhs.duke.edu/software.

Suggested Citation

  • Schmidt Mike & Hauser Elizabeth R & Martin Eden R. & Schmidt Silke, 2005. "Extension of the SIMLA Package for Generating Pedigrees with Complex Inheritance Patterns: Environmental Covariates, Gene-Gene and Gene-Environment Interaction," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 4(1), pages 1-22, June.
    • Handle: RePEc:bpj:sagmbi:v:4:y:2005:i:1:n:15
    DOI: 10.2202/1544-6115.1133
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    Citations

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    Cited by:

    1. Arafat Tayeb & Aurélie Labbe & Alexandre Bureau & Chantal Mérette, 2011. "Solving genetic heterogeneity in extended families by identifying sub-types of complex diseases," Computational Statistics, Springer, vol. 26(3), pages 539-560, September.
    2. Crosslin David R. & Qin Xuejun & Hauser Elizabeth R., 2010. "Assessment of LD Matrix Measures for the Analysis of Biological Pathway Association," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 9(1), pages 1-46, October.
    3. Labbe Aurelie & Bureau Alexandre & Merette Chantal, 2009. "Integration of Genetic Familial Dependence Structure in Latent Class Models," The International Journal of Biostatistics, De Gruyter, vol. 5(1), pages 1-30, January.

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