1. ¹Human Medical Genetics Program, University of Colorado Denver, Aurora, Colorado, USA
2. ²Department of Dermatology, University of Colorado Denver, Aurora, Colorado, USA
3. ³Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA
4. ⁴Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA

Correspondence: Richard A. Spritz, Human Medical Genetics Program, University of Colorado Denver, Anschutz Medical Campus, PO Box 6511, MS 8300, Aurora, Colorado 80045, USA. E-mail: Richard.Spritz@ucdenver.edu

Received 28 July 2009; Revised 16 September 2009; Accepted 23 September 2009; Published online 5 November 2009.

Abstract

Generalized vitiligo is a common disorder in which patchy loss of skin and hair pigmentation principally appears to result from autoimmune loss of melanocytes from affected regions. We previously characterized a unique founder population in an isolated Romanian community with elevated prevalence of generalized vitiligo and other autoimmune diseases, including autoimmune thyroid disease, rheumatoid arthritis, and type I diabetes mellitus. Here, we describe a genome-wide association study (GWAS) of generalized vitiligo in 32 distantly related affected patients from this remote village and 50 healthy controls from surrounding villages. Vitiligo was significantly associated with single-nucleotide polymorphisms (SNPs) in a 30-kb LD block on chromosome 6q27, in close vicinity to IDDM8, a linkage and association signal for type I diabetes mellitus and rheumatoid arthritis. The region of association contains only one gene, SMOC2, within which SNP rs13208776 attained genome-wide significance for association with generalized vitiligo (P=8.51 10^-8) at odds ratio 7.445 (95% confidence interval=3.56–15.53) for the high-risk allele and population attributable risk 28.00. SMOC2 encodes a modular extracellular calcium-binding glycoprotein of unknown function. Our findings indicate that SMOC2 is a risk locus for generalized vitiligo and perhaps other autoimmune diseases.