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X-chromosome genetic association test incorporating X-chromosome inactivation and imprinting effects

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Abstract

Studies have shown that many complex diseases are sex-determined. When conducting genetic association studies on X-chromosome, there are two important epigenetic factors which should be considered simultaneously: X-chromosome inactivation and genomic imprinting. Currently, there have been several association tests accounting for the information on X-chromosome inactivation. However, these tests do not take the imprinting effects into account. In this paper, we propose a novel association test simultaneously incorporating X-chromosome inactivation and imprinting effects based on case–parent trios and control–parent trios for female offspring and case–control data for male offspring, denoted by \( MLR_{XCII} \). Extensive simulation studies are carried out to investigate the type I error rate and the test power of the proposed \( MLR_{XCII} \). Simulation results demonstrate that the proposed test controls the type I error rate well and is more powerful than the existing method when imprinting effects exist. The proposed \( MLR_{XCII} \) test is valid and powerful in genetic association studies on X-chromosome for qualitative traits and thus is recommended in practice.

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Acknowledgements

The authors thank the two reviewers for helpful comments that greatly improve the presentation of the paper. This work was supported by the National Natural Science Foundation of China (grant 81773544), the National and Guangzhou University Students’ Innovation and Enterprise Training Project of China (grant 201712121105) and the Hong Kong RGC GRF grant (17302919).

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Authors and Affiliations

  1. State Key Laboratory of Organ Failure Research, Ministry of Education, and Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China

    Wei Liu, Bei-Qi Wang, Guojun Liu-Fu & Ji-Yuan Zhou

  2. Faculty of Science, Department of Statistics and Actuarial Science, The University of Hong Kong, Pok Fu Lam, Hong Kong, People’s Republic of China

    Wing Kam Fung

Authors
  1. Wei Liu
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  2. Bei-Qi Wang
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  3. Guojun Liu-Fu
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  4. Wing Kam Fung
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  5. Ji-Yuan Zhou
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Corresponding authors

Correspondence to Wing Kam Fung or Ji-Yuan Zhou.

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Corresponding editor: H. A. Ranganath

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Liu, W., Wang, BQ., Liu-Fu, G. et al. X-chromosome genetic association test incorporating X-chromosome inactivation and imprinting effects. J Genet 98, 99 (2019). https://doi.org/10.1007/s12041-019-1146-6

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  • DOI: https://doi.org/10.1007/s12041-019-1146-6

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