Abstract
For qualitative traits and diallelic marker loci, the pedigree disequilibrium test (PDT) based on general pedigrees and its extension (Monte Carlo PDT (MCPDT)) for dealing with missing genotypes are simple and powerful tests for association. There is an increasing interest of incorporating imprinting into association analysis. However, PDT and MCPDT do not take account of the information on imprinting effects in the analysis, which may reduce their test powers when the effects are present. On the other hand, the transmission disequilibrium test with imprinting (TDTI*) combines imprinting into the mapping of association variants. However, TDTI* only accommodates two-generation nuclear families and thus is not suitable for extended pedigrees. In this article, we first extend PDT to incorporate imprinting and propose PDTI for complete pedigrees (no missing genotypes). To fully utilize pedigrees with missing genotypes, we further develop the Monte Carlo PDTI (MCPDTI) statistic based on Monte Carlo sampling and estimation. Both PDTI and MCPDTI are derived in a two-stage framework. Simulation study shows that PDTI and MCPDTI control the size well under the null hypothesis of no association and are more powerful than PDT and TDTI* (based on a sample of nuclear families randomly selecting from pedigrees) when imprinting effects exist.
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Acknowledgements
We thank the Associate Editor and two reviewers for their insightful and helpful suggestions, which have led to improvement of the presentation. This work was supported by the National Natural Science Foundation of China (grants 81373098 and 81072386), Science and Technology Planning Project of Guangdong Province, China (grant 2013B021800038), the National and Guangdong University Students’ Innovation and Enterprise Training Project of China (grants 201312121014 and 1212113029), grant from School of Public Health and Tropical Medicine of Southern Medical University, China (grant GW201422) and the Hong Kong RGC GRF Research Grant (HKU 766511M). We are also grateful to Dr Jie Ding who shares his R code with us.
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Zhou, JY., He, HQ., You, XP. et al. A powerful association test for qualitative traits incorporating imprinting effects using general pedigree data. J Hum Genet 60, 77–83 (2015). https://doi.org/10.1038/jhg.2014.109
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DOI: https://doi.org/10.1038/jhg.2014.109
