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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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.

Author information

Affiliations

  1. Human Medical Genetics Program, University of Colorado School of Medicine, Aurora, Colorado, USA.

    • Ying Jin
    • , Stanca A Birlea
    • , Pamela R Fain
    • , Tracey M Ferrara
    • , Songtao Ben
    • , Sheri L Riccardi
    • , Joanne B Cole
    • , Katherine Gowan
    • , Paulene J Holland
    •  & Richard A Spritz
  2. Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.

    • Ying Jin
    • , Pamela R Fain
    •  & Richard A Spritz
  3. Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA.

    • Stanca A Birlea
  4. Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado, USA.

    • Pamela R Fain
  5. Division of Biomedical Sciences, St. George's, University of London, London, UK.

    • Dorothy C Bennett
  6. Department of Dermatology and the Netherlands Institute for Pigment Disorders, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

    • Rosalie M Luiten
    • , Albert Wolkerstorfer
    •  & J P Wietze van der Veen
  7. Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.

    • Anke Hartmann
    • , Saskia Eichner
    •  & Gerold Schuler
  8. Department of Dermatology, Ghent University Hospital, Ghent, Belgium.

    • Nanja van Geel
    •  & Jo Lambert
  9. Department of Human Metabolism, School of Medicine, University of Sheffield, Sheffield, UK.

    • E Helen Kemp
    •  & Anthony P Weetman
  10. Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK.

    • David J Gawkrodger
  11. Centre de Référence des Maladies Rares de la peau, Department of Dermatology, Hôpital St-André, Bordeaux, France.

    • Alain Taïeb
    • , Thomas Jouary
    •  & Khaled Ezzedine
  12. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.

    • Margaret R Wallace
  13. Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.

    • Wayne T McCormack
  14. Laboratorio Fisiopatologia Cutanea, Istituto Dermatologico San Gallicano, Rome, Italy.

    • Mauro Picardo
    •  & Giovanni Leone
  15. Lumiderm, Madrid, Spain.

    • Andreas Overbeck
  16. Department of Dermatology, Columbia University College of Physicians and Surgeons, New York, New York, USA.

    • Nanette B Silverberg
  17. Pediatric and Adolescent Dermatology, St. Luke's-Roosevelt Hospital Center, New York, New York, USA.

    • Nanette B Silverberg

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Richard A Spritz.

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DOI

https://doi.org/10.1038/ng.2272

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