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

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.

SUBMITTER: Zuo XY 

PROVIDER: S-EPMC6434801 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature