An in-depth analysis reveals two new genetic variants on 22q11.2 associated with vitiligo in the Chinese Han population

Background Vitiligo is a complex disease in which patchy depigmentation is the result of an autoimmune-induced loss of melanocytes in affected regions. On the basis of a genome-wide linkage analysis of vitiligo in the Chinese Han population, we previously showed significant evidence of a linkage between 22q12 and vitiligo. Our aim in the current study was to identify vitiligo susceptibility variants within an expanded region of the 22q12 locus. Methods and results An in-depth analysis of the expanded region of the 22q12 locus was performed by imputation using a large GWAS dataset consisting of 1117 cases and 1701 controls. Eight nominal SNPs were selected and genotyped in an independent cohort of Chinese Han individuals (2069 patients and 1370 control individuals) by using the Sequenom MassArray iPLEX1 system. The data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R showed a strong association with vitiligo ( P = 3.25 × 10 –8 , OR = 0.81). The C allele of rs4820338 located in VPREB1 and the A allele of rs2051582 (a SNP reported in our previous study) located in IL2RB showed a suggestive association with vitiligo ( 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 in a conditional logistic regression analysis (all P < 1.0 × 10 –5 ; all D′ < 0.05 and r 2 < 1.0 × 10 –4 ). Conclusions The study reveals that two novel variants rs730669 ( ZDHHC8/RTN4R ) and rs4820338 ( VPREB1 ) on 22q11.2 might confer susceptibility to vitiligo and affect disease subphenotypes. The presence of multiple independent variants emphasizes their important roles in the genetic pathogenesis of disease.