An in-Depth Analysis Identifies Two New Genetic Variants in 22q11.2 Associated with Vitiligo in the Chinese Han Population

Abstract Background Vitiligo is a complex disease in which patchy depigmentation results from autoimmune loss of melanocytes in affected regions. Previously, we provided significant linkage evidence on 22q12 by genomewide linkage analysis of vitiligo in the Chinese Han population. Our aim is to identify susceptibility variants associated with vitiligo at an expanded region for 22q12. Methods and Results A deep analysis of the expanded region for 22q12 locus was performed in a large GWAS dataset consisting of 1117 cases and 1701 controls by imputation. Eight nominal SNPs were selected and genotyped in an independent cohort of 2069 cases and 1370 controls of Chinese Han by using the Sequenom MassArray iPLEX1 system. Data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R was observed a strong evidence of association for vitiligo (P = 3.25×10-8, OR = 0.81). The C allele of rs4820338 located in VPREB1 and A allele of rs2051582 (a reported SNP in our previous study) located in IL2RB were suggestive evidence of association for vitligo (P = 1.04×10-5, OR = 0.86; P = 1.78×10-6, OR = 1.27). The three identified SNPs showed independent associations with vitiligo by conditional logistic regression (all P < 1.0 ×10-5; all D′< 0.05, r 2 < 0.0001). Conclusions The study identifies that two novel variants rs730669 (ZDHHC8/RTN4R) and rs4820338 (VPREB1) in 22q11.2 might confer susceptibility to vitiligo and affect its disease phenotypes. The presence of multiple independent variants emphasizes an important role in the genetic pathogenesis of disease.