title: Parameter estimation and quantitative parametric linkage analysis with GENEHUNTER-QMOD.
abstract: OBJECTIVE
  We present 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. We have implemented our new method in the program GENEHUNTER-QMOD and evaluated its properties by performing simulations.
  
  
  METHODS
  The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype. Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called PGRAD method.
  
  
  RESULTS
  The PGRAD method has lower power to detect linkage than the variance components analysis (VCA) in case of a normal distribution and small pedigrees. However, it outperforms the VCA and Haseman-Elston regression for extended pedigrees, nonrandomly ascertained data and non-normally distributed phenotypes. Here, the higher power even goes along with conservativeness, while the VCA has an inflated type I error. Parameter estimation tends to underestimate residual variances but performs better for expectation values of the phenotype distributions.
  
  
  CONCLUSIONS
  With GENEHUNTER-QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes in the context of linkage analysis. It is freely available at http://www.helmholtz-muenchen.de/genepi/downloads.
authors.affiliation: Institute of Medical Biometry and Epidemiology, Philipps University Marburg, Marburg, Germany. thomas.kuenzel@accovion.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Künzel
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
mesh_terms: D000465:Algorithms; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005828:Genetics, Population / Q000379:methods; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci; D012984:Software