title: Genome-wide association study of generalized vitiligo in an isolated European founder population identifies SMOC2, in close proximity to IDDM8.
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=8.51x10(-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.
authors.affiliation: Human Medical Genetics Program, Department of Dermatology, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Stanca A
authors.initials: SA
authors.lastname: Birlea
authors.forename: Katherine
authors.initials: K
authors.lastname: Gowan
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D018703:Founder Effect; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012383:Romania / Q000453:epidemiology; D014820:Vitiligo / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D002135:Calcium-Binding Proteins; C476827:SMOC2 protein, human