Visual Universitätsmedizin Mainz

GENEHUNTER-QMOD

GENEHUNTER-QMOD is an extension of the GENEHUNTER software package (Kruglyak et al. 1996; Kruglyak and Lander 1998; Markianos et al. 2001) that enables a parametric method for linkage analysis of quantitative phenotypes. The method provides a test for linkage as well as an estimate of different phenotype parameters. The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype, as depicted in the figure below (see also Künzel & Strauch, 2012):

graph3.png

Where fi denotes the probability density function of the quantitative phenotype given a certain genotype i, with + and m corresponding to the wild-type and mutant allele in the case of dichotomous trait locus, respectively. Each density function describes the distribution of the quantitative phenotype of individuals with one of the following genotypes: (+,+), (m ,+) or (m,m). Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called projected-gradient (PGRAD) method.

Hence, the parameters of the trait model consist of the corresponding expectation values of the normal distributions and the corresponding standard deviations as well as the disease allele frequency. The quantitative LOD score is maximized over the phenotype parameters by the PGRAD optimization, therefore yielding the MOD score. It is possible to adapt the trait model to imprinting, no-dominance effects and equal residual variances.

Empirical p-values can be calculated with the method implemented in GENEHUNTER-MODSCORE. Furthermore, it is possible to calculate p-values with a technique called 'sample method', which yields approximately the same p-values as with the PGRAD optimization, but is much faster.

More information about GENEHUNTER-QMOD can be found in the file INSTALL.ghm that is included in the archives provided below.

Reference publication for GENEHUNTER-QMOD:

  • Künzel, T & Strauch K (2012): Parameter estimation and quantitative parametric linkage analysis with GENEHUNTER-QMOD. Human Heredity 73:208-219

Original GENEHUNTER references:

  • Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES (1996): Parametric and nonparametric linkage analysis: a unified multipoint approach. American Journal of Human Genetics 58:1347-1363
  • Kruglyak L, Lander ES (1998): Faster multipoint linkage analysis using Fourier transforms. Journal of Computational Biology 5:1-7
  • Markianos K, Daly MJ, Kruglyak L (2001): Efficient multipoint linkage analysis through reduction of inheritance space. American Journal of Human Genetics 68:963-977

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