Genetic imprinting, or called the parent-of-origin effect, has been recognized to play an important role in the formation and pathogenesis of human diseases. Although the epigenetic mechanisms that establish genetic imprinting have been a focus of many genetic studies, our knowledge about the number of imprinting genes and their chromosomal locations and interactions with other genes is still scarce, limiting precise inference of the genetic architecture of complex diseases. In this article, we present a statistical model for testing and estimating the effects of genetic imprinting on complex diseases using a commonly used case-control design with family structure. For each subject sampled from a case and control population, we not only genotype its own single nucleotide polymorphisms (SNPs) but also collect its parents' genotypes. By tracing the transmission pattern of SNP alleles from parental to offspring generation, the model allows the characterization of genetic imprinting effects based on Pearson tests of a 2 × 2 contingency table. The model is expanded to test the interactions between imprinting effects and additive, dominant and epistatic effects in a complex web of genetic interactions. Statistical properties of the model are investigated, and its practical usefulness is validated by a real data analysis. The model will provide a useful tool for genome-wide association studies aimed to elucidate the picture of genetic control over complex human diseases.
Functional Mapping is a popular statistical method in QTL mapping studies for longitudinal data. The threshold for declaring statistical significance of a QTL is commonly obtained through permutation tests, which can be time consuming. To improve the computational efficiency of a permutation test of mixture models used in Functional Mapping, we first quantified the correlation between QTL and longitudinal data, using a curve clustering method. Then, the QTLs which are highly correlated with the outcome were computed in the improved permutation tests. As a result, it reduces the amount of computation in permutation tests and speeds up the computation for Functional Mapping analysis. Simulation studies and real data analysis were conducted to demonstrate that the proposed approach can greatly improve the computational efficiency of QTL mapping without loss of accuracy.
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