Cheng Lu, Liang Bo, Tang Xian-Fa, Cai Xin-Ying, Cheng Hui, Zheng Xiao-Dong, Zheng Jie, Wang Meng-Wei, Zhu Jun, Zhou Fu-Sheng, Li Pan, Xiao Feng-Li
Department of Dermatology of First Affiliated Hospital, Institute of Dermatology, Anhui Medical University, Hefei, China.
Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, China.
Front Genet. 2020 Dec 3;11:542275. doi: 10.3389/fgene.2020.542275. eCollection 2020.
Forty-nine susceptible loci have been reported to be significantly associated with vitiligo by genome-wide association studies (GWASs) in European-derived whites. To date, some of these reported susceptibility loci have not yet been validated in the Chinese Han population. The purpose of this study was to examine whether the 16 reported susceptible loci in European-derived whites were associated with vitiligo in the Chinese Han population. Imputation was performed using our previous GWAS dataset by IMPUTE v2.2.2. The 16 imputed top single-nucleotide polymorphisms (SNPs) with suggestive signals, together with the reported SNPs, were genotyped in a total of 2581 patients and 2579 controls by the Sequenom MassARRAY system. PLINK 2.0 software was used to perform association analysis. The dbSNP database, HaploReg, and eQTL data were adopted to annotate the biological function of the SNPs. Finally, four SNPs from three loci were significantly associated with vitiligo, including rs3747517 ( = 1.29 × 10, OR = 0.87) in 2q24.2, rs4807000 ( = 7.78 × 10, OR = 0.66) and rs6510827 ( = 3.65 × 10, OR = 1.19) in 19p13.3, and rs4822024 ( = 6.37 × 10, OR = 0.67) in 22q13.2. According to the dbSNP database, rs3747517 is a missense variant of , rs4807000 and rs6510827 are located in , and rs4822024 is located 6 kb upstream of . Further bioinformatics analysis by HaploReg and eQTL found that rs4807000, rs6510827, and rs4822024 are involved in regulating gene expression. Our study revealed the strong association of 2q24.2 (rs3747517), 19p13.3 (rs4807000, rs6510827), and 22q13.2 (rs4822024) with the risk of vitiligo in the Chinese Han population, which implicates common factors for vitiligo across different ethnicities, and helps expand the understanding of the genetic basis of this disease.
通过全基因组关联研究（GWAS），在欧洲裔白人中已报道有49个易感基因座与白癜风显著相关。迄今为止，其中一些报道的易感基因座尚未在中国汉族人群中得到验证。本研究的目的是检验在欧洲裔白人中报道的16个易感基因座是否与中国汉族人群的白癜风相关。使用IMPUTEv2.2.2软件，根据我们之前的GWAS数据集进行基因填充。通过Sequenom MassARRAY系统，对16个推测的具有提示性信号的顶级单核苷酸多态性（SNP）以及报道的SNP，在总共2581例患者和2579例对照中进行基因分型。使用PLINK 2.0软件进行关联分析。采用dbSNP数据库、HaploReg和eQTL数据注释SNP的生物学功能。最后，来自3个基因座的4个SNP与白癜风显著相关，包括2q24.2区域的rs3747517（P = 1.29×10⁻⁶，OR = 0.87）、19p13.3区域的rs4807000（P = 7.78×10⁻⁶，OR = 0.66）和rs6510827（P = 3.65×10⁻⁵，OR = 1.19），以及22q13.2区域的rs4822024（P = 6.37×10⁻⁵，OR = 0.67）。根据dbSNP数据库，rs3747517是[基因名称]的错义变异，rs4807000和rs6510827位于[基因名称]内，rs4822024位于[基因名称]上游6 kb处。通过HaploReg和eQTL进行的进一步生物信息学分析发现，rs4807000、rs6510827和rs4822024参与调节基因表达。我们的研究揭示了2q24.2（rs3747517）、19p13.3（rs4807000，rs6510827）和22q13.2（rs4822024）与中国汉族人群白癜风风险的强关联，这暗示了不同种族间白癜风的共同因素，并有助于扩展对该疾病遗传基础的理解。
