X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma
Document Type
Article
Publication Date
1-1-2019
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.
Keywords
Association study, Genetic susceptibility, Male predominance, Nasopharyngeal carcinoma, X chromosome
Divisions
InstituteofBiologicalSciences
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]
Publication Title
Biology of Sex Differences
Volume
10
Issue
1
Publisher
BMC