title: Fast linkage analysis with MOD scores using algebraic calculation.
abstract: OBJECTIVE
  As the mode of inheritance is often unknown for complex diseases, a MOD-score analysis, in which the parametric LOD score is maximized with respect to the trait-model parameters, can be a powerful approach in genetic linkage analysis. Because the calculation of the disease-locus likelihood is the most time-consuming step in a MOD-score analysis, we aimed to optimize this part of the calculation to speed up linkage analysis using the GENEHUNTER-MODSCORE software package.
  
  
  METHODS
  Our new algorithm is based on minimizing the effective number of inheritance vectors by collapsing them into classes. To this end, the disease-locus-likelihood contribution of each inheritance vector is represented and stored in its algebraic form as a symbolic sum of products of penetrances and disease-allele frequencies. Simulations were used to assess the speedup of our new algorithm.
  
  
  RESULTS
  We were able to achieve speedups ranging from 1.94 to 11.52 compared to the original GENEHUNTER-MODSCORE version, with higher speedups for larger pedigrees. When calculating p values, the speedup ranged from 1.69 to 10.36.
  
  
  CONCLUSIONS
  Computation times for MOD-score analysis, involving the evaluation of many tested sets of trait-model parameters and p value calculation, have been prohibitively high so far. With our new algebraic algorithm, such an analysis is now feasible within a reasonable amount of time.
authors: Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, and Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors: Markus
authors: M
authors: Brugger
authors: Konstantin
authors: K
authors: Strauch
mesh_terms: D000465:Algorithms; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D040941:Heredity; D006801:Humans; D008390:Markov Chains; D010375:Pedigree; D012984:Software