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Open Access Green as soon as Postprint is submitted to ZB.
Fast linkage analysis with MOD scores using algebraic calculation.
Hum. Hered. 78, 179-194 (2014)
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. CONCLUSION: 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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Parametric Linkage Analysis ; Mod Scores ; Lander-green Algorithm ; Algebraic Calculation ; Rare Variants; Statistical Genetic-analysis; Lod Score; Likelihood Calculations; Genehunter-modscore; Large Pedigrees; Multipoint; Inheritance; Algorithm; Locus; Tests
ISSN (print) / ISBN
0001-5652
e-ISSN
1423-0062
Journal
Human Heredity
Quellenangaben
Volume: 78,
Issue: 3-4,
Pages: 179-194
Publisher
Karger
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Genetic Epidemiology (IGE)