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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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

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. More... »

PAGES

13

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13293-019-0227-9

    DOI

    http://dx.doi.org/10.1186/s13293-019-0227-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112986566

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30909962


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