Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo

Ying Jin, Stanca A Birlea, Pamela R Fain, Tracey M Ferrara, Songtao Ben, Sheri L Riccardi, Joanne B Cole, Katherine Gowan, Paulene J Holland, Dorothy C Bennett, Rosalie M Luiten, Albert Wolkerstorfer, J P Wietze van der Veen, Anke Hartmann, Saskia Eichner, Gerold Schuler, Nanja van Geel, Jo Lambert, E Helen Kemp, David J Gawkrodger, Anthony P Weetman, Alain Taïeb, Thomas Jouary, Khaled Ezzedine, Margaret R Wallace, Wayne T McCormack, Mauro Picardo, Giovanni Leone, Andreas Overbeck, Nanette B Silverberg, Richard A Spritz, Ying Jin, Stanca A Birlea, Pamela R Fain, Tracey M Ferrara, Songtao Ben, Sheri L Riccardi, Joanne B Cole, Katherine Gowan, Paulene J Holland, Dorothy C Bennett, Rosalie M Luiten, Albert Wolkerstorfer, J P Wietze van der Veen, Anke Hartmann, Saskia Eichner, Gerold Schuler, Nanja van Geel, Jo Lambert, E Helen Kemp, David J Gawkrodger, Anthony P Weetman, Alain Taïeb, Thomas Jouary, Khaled Ezzedine, Margaret R Wallace, Wayne T McCormack, Mauro Picardo, Giovanni Leone, Andreas Overbeck, Nanette B Silverberg, Richard A Spritz

Abstract

We previously reported a genome-wide association study (GWAS) identifying 14 susceptibility loci for generalized vitiligo. We report here a second GWAS (450 individuals with vitiligo (cases) and 3,182 controls), an independent replication study (1,440 cases and 1,316 controls) and a meta-analysis (3,187 cases and 6,723 controls) identifying 13 additional vitiligo-associated loci. These include OCA2-HERC2 (combined P = 3.80 × 10(-8)), MC1R (P = 1.82 × 10(-13)), a region near TYR (P = 1.57 × 10(-13)), IFIH1 (P = 4.91 × 10(-15)), CD80 (P = 3.78 × 10(-10)), CLNK (P = 1.56 × 10(-8)), BACH2 (P = 2.53 × 10(-8)), SLA (P = 1.58 × 10(-8)), CASP7 (P = 3.56 × 10(-8)), CD44 (P = 1.78 × 10(-9)), IKZF4 (P = 2.75 × 10(-14)), SH2B3 (P = 3.54 × 10(-18)) and TOB2 (P = 6.81 × 10(-10)). Most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and the relationships among vitiligo, melanoma, and eye, skin and hair coloration.

Figures

Figure 1
Figure 1
Association of generalized vitiligo with SNPs in the OCA2-HERC2 region of chromosome 15q12–q13.1. Results of Cochran-Mantel-Haenszel meta-analysis of GWAS1 and GWAS2 data (GWAS-MA) for genotyped (black) and imputed (blue) SNPs on the y axis versus chromosomal nucleotide position (GRCh37/hg19) on the x axis. Red circles indicate the Cochran-Mantel-Haenszel P values from the GWAS1, GWAS2, and replication studies for rs12913832 and rs1129038 (see Table 1). Arrows indicate gene positions and transcriptional orientation.

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