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 u...
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2019-03-01
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Series: | Biology of Sex Differences |
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Online Access: | http://link.springer.com/article/10.1186/s13293-019-0227-9 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma Biology of Sex Differences Nasopharyngeal carcinoma Genetic susceptibility X chromosome Association study Male predominance |
author_facet |
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 |
author_sort |
Xiao-Yu Zuo |
title |
X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma |
title_short |
X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma |
title_full |
X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma |
title_fullStr |
X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma |
title_full_unstemmed |
X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma |
title_sort |
x-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma |
publisher |
BMC |
series |
Biology of Sex Differences |
issn |
2042-6410 |
publishDate |
2019-03-01 |
description |
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. |
topic |
Nasopharyngeal carcinoma Genetic susceptibility X chromosome Association study Male predominance |
url |
http://link.springer.com/article/10.1186/s13293-019-0227-9 |
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doaj-38e8451dc36b44588032740922b7d6f02020-11-25T02:10:02ZengBMCBiology of Sex Differences2042-64102019-03-0110111110.1186/s13293-019-0227-9X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinomaXiao-Yu Zuo0Qi-Sheng Feng1Jian Sun2Pan-Pan Wei3Yoon-Ming Chin4Yun-Miao Guo5Yun-Fei Xia6Bo Li7Xiao-Jun Xia8Wei-Hua Jia9Jian-Jun Liu10Alan Soo-Beng Khoo11Taisei Mushiroda12Ching-Ching Ng13Wen-Hui Su14Yi-Xin Zeng15Jin-Xin Bei16State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterInstitute of Biological Sciences, Faculty of Science, University of MalayaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterDepartment of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-Sen UniversityState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterHuman Genetics, Genome Institute of Singapore, Agency for Science, Technology, and ResearchMolecular Pathology Unit, Cancer Research Centre, Institute for Medical ResearchLaboratory for International Alliance on Genomic Research, RIKEN Center for Integrative Medical SciencesInstitute of Biological Sciences, Faculty of Science, University of MalayaDepartment of Biomedical Sciences, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung Molecular Medicine Research Center, Chang Gung UniversityState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterAbstract 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.http://link.springer.com/article/10.1186/s13293-019-0227-9Nasopharyngeal carcinomaGenetic susceptibilityX chromosomeAssociation studyMale predominance |