Zuo, Xiao-Yu and Feng, Qi-Sheng and Sun, Jian and Wei, Pan-Pan and Chin, Yoon Ming and Guo, Yun-Miao and Xia, Yun-Fei and Li, Bo and Xia, Xiao-Jun and Jia, Wei-Hua and Liu, Jian-Jun and Khoo, Alan Soo-Beng and Mushiroda, Taisei and Ng, Ching Ching and Su, Wen-Hui and Zeng, Yi-Xin and Bei, Jin-Xin (2019) X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma. Biology of Sex Differences, 10 (1). p. 13. ISSN 2042-6410, DOI https://doi.org/10.1186/s13293-019-0227-9.
Full text not available from this repository.Abstract
Background: The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far. Methods: To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716). Results: Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73-0.89, P = 1.49 × 10 -5 ). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10 -5 ). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47-0.81, P = 4.37 × 10 -4 ) was successfully replicated in Taiwan Chinese (P = 1.64 × 10 -2 ). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10 -4 ) and Taiwan datasets (P = 2.99 × 10 -2 ). Conclusion: Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.
| Item Type: | Article |
|---|---|
| Funders: | National Key Research and Development Program of China [2016YFC0902001], National High Technology Research and Development Program of China [2012AA02A206], National Natural Science Foundation of China [81572781, 81602478, 81372882, 81222035], China Postdoctoral Science Foundation [2015 M580759], Natural Science Foundation of Guangdong Province [2016A030310194], Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S638], Program for New Century Excellent Talents in University [NCET-11-0529] |
| Uncontrolled Keywords: | Association study; Genetic susceptibility; Male predominance; Nasopharyngeal carcinoma; X chromosome |
| Subjects: | Q Science > Q Science (General) Q Science > QH Natural history |
| Divisions: | Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 31 Oct 2019 03:06 |
| Last Modified: | 31 Oct 2019 03:06 |
| URI: | http://eprints.um.edu.my/id/eprint/22883 |
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