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    Keywords: Germany ; MODEL ; DISEASE ; GENE ; SAMPLE ; IMPACT ; ASSOCIATION ; FREQUENCIES ; PERFORMANCE ; genetics ; RATES ; REPLICATION ; UNCERTAINTY ; transmission/disequilibrium test ; TESTS ; ERROR ; HARDY-WEINBERG EQUILIBRIUM ; ROBUST ; CONTROL GENETIC ASSOCIATION ; MISCLASSIFICATION ; TAGGING SNP SELECTION
    Abstract: Background: We investigated the influence of genotyping errors on the type I error rate and empirical power of two haplotype based association methods applied to candidate regions. We compared the performance of the Mantel Statistic Using Haplotype Sharing and the haplotype frequency based score test with that of the Armitage trend test. Our study is based on 1000 replication of simulated case-control data settings with 500 cases and 500 controls, respectively. One of the examined markers was set to be the disease locus with a simulated odds ratio of 3. Differential and non-differential genotyping errors were introduced following a misclassification model with varying mean error rates per locus in the range of 0.2% to 15.6%. Results: We found that the type I error rate of all three test statistics hold the nominal significance level in the presence of nondifferential genotyping errors and low error rates. For high and differential error rates, the type I error rate of all three test statistics was inflated, even when genetic markers not in Hardy-Weinberg Equilibrium were removed. The empirical power of all three association test statistics remained high at around 89% to 94% when genotyping error rates were low, but decreased to 48% to 80% for high and nondifferential genotyping error rates. Conclusion: Currently realistic genotyping error rates for candidate gene analysis (mean error rate per locus of 0.2%) pose no significant problem for the type I error rate as well as the power of all three investigated test statistics
    Type of Publication: Journal article published
    PubMed ID: 19178712
    Signatur Availability
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