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Brugger, M. ; Rospleszcz, S. ; Strauch, K.

Estimation of trait-model parameters in a MOD score linkage analysis.

Hum. Hered. 82, 103-139 (2016)

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BACKGROUND/AIMS: Theoretically, the trait-model parameters (disease allele frequency and penetrance function) can be estimated without bias in a MOD score linkage analysis. We aimed to practically evaluate the MOD score approach regarding its ability to provide unbiased trait-model parameters for various pedigree-type and trait-model scenarios. We further investigated the ability of the MOD score approach to detect imprinting using affected sib pairs (ASPs) and affected half-sib pairs (AHSPs) when all parental genotypes are missing. METHODS: Simulated pedigree data were analyzed using the GENEHUNTER-MODSCORE software package. Parameter estimation performance in terms of bias and variability was evaluated with regard to trait-model type and pedigree complexity. RESULTS: Generally, parameters were estimated with lower bias and variability with increasing pedigree complexity, especially for recessive and overdominant models. However, dominant and additive models could hardly be distinguished even when using 3-generation pedigrees. Imprinting could clearly be detected for mixtures of mainly ASPs and only few AHSPs with the common parent of the imprinted sex, even though no parental genotypes were available. CONCLUSION: Our results provide guidance to researchers regarding the possibility to estimate trait-model parameters by a MOD score analysis, including the degree of imprinting, with certain types of pedigrees.

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