X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma

Xiao Yu Zuo, Qi Sheng Feng, Jian Sun, Pan Pan Wei, Yoon Ming Chin, Yun Miao Guo, Yun Fei Xia, Bo Li, Xiao Jun Xia, Wei Hua Jia, Jian Jun Liu, Alan Soo Beng Khoo, Taisei Mushiroda, Ching Ching Ng*, Wen Hui Su, Yi Xin Zeng, Jin Xin Bei

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

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.

Original languageEnglish
Article number13
JournalBiology of Sex Differences
Volume10
Issue number1
DOIs
StatePublished - 25 03 2019

Bibliographical note

Publisher Copyright:
© 2019 The Author(s).

Keywords

  • Association study
  • Genetic susceptibility
  • Male predominance
  • Nasopharyngeal carcinoma
  • X chromosome

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