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

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.

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Figure 1: Association of generalized vitiligo with SNPs in the OCA2-HERC2 region of chromosome 15q12-q13.1.

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Acknowledgements

We thank the many patients with vitiligo and healthy control individuals around the world who participated in this study. We thank the University of Colorado Cancer Center Genomics and Microarray Core for genome-wide genotyping and BodySync (Aurora, Colorado, USA) for replication genotyping. This work was supported by grants R01AR045584, R01AR056292 and P30AR057212 from the U.S. National Institutes of Health.

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Y.J. performed statistical analyses. K.G. managed computer databases and genotype data. T.M.F., S.B., S.A.B., S.L.R. and J.B.C. managed DNA samples and contributed to experimental procedures. P.J.H. managed subject coordination. S.A.B., D.C.B., R.M.L., A.W., J.P.W.v.d.V., M.R.W., W.T.M., E.H.K., D.J.G., A.P.W., M.P., G.L., A.T., T.J., K.E., N.v.G., J.L., A.O., A.H., S.E., G.S. and N.B.S. provided subject samples and phenotype information. P.R.F. and R.A.S. oversaw and managed all aspects of the study. R.A.S. wrote the first draft of the manuscript. All authors contributed to the final paper.

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Correspondence to Richard A Spritz.

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The authors declare no competing financial interests.

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Jin, Y., Birlea, S., Fain, P. et al. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat Genet 44, 676–680 (2012). https://doi.org/10.1038/ng.2272

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