Generalized vitiligo is an autoimmune disease in which melanocyte loss results in patchy depigmentation of skin and hair. For this GWAS of generalized vitiligo, 579,146 SNPs were genotyped in 1514 generalized vitiligo cases of European-derived white (CEU) ancestry versus data from 2813 "public" CEU controls. 49 strongly associated SNPs from the first phase of the GWAS were then tested in two replication studies, one comparing 677 independent cases and 1106 CEU controls, and the other a family-based analysis of 204 CEU simplex generalized vitiligo trios and 310 CEU multiplex families. Overall, significant association of generalized vitiligo was detected for SNPs in several genes previously associated with other autoimmune diseases, including MHC class I (P = 9.05 x 10^-23) and class II (P = 4.50 x 10^-34) loci, PTPN22 (P = 1.31 x 10^-7), LPP (P = 1.01 x 10^-11), IL2RA (P = 2.78 x 10^-9), UBASH3A (P = 1.26 x 10^-9), and C1QTNF6 (P = 2.21 x 10^-16). Association was also detected for SNPs in two novel ... (Show More)

Generalized vitiligo is an autoimmune disease in which melanocyte loss results in patchy depigmentation of skin and hair. For this GWAS of generalized vitiligo, 579,146 SNPs were genotyped in 1514 generalized vitiligo cases of European-derived white (CEU) ancestry versus data from 2813 "public" CEU controls. 49 strongly associated SNPs from the first phase of the GWAS were then tested in two replication studies, one comparing 677 independent cases and 1106 CEU controls, and the other a family-based analysis of 204 CEU simplex generalized vitiligo trios and 310 CEU multiplex families. Overall, significant association of generalized vitiligo was detected for SNPs in several genes previously associated with other autoimmune diseases, including MHC class I (P = 9.05 x 10^-23) and class II (P = 4.50 x 10^-34) loci, PTPN22 (P = 1.31 x 10^-7), LPP (P = 1.01 x 10^-11), IL2RA (P = 2.78 x 10^-9), UBASH3A (P = 1.26 x 10^-9), and C1QTNF6 (P = 2.21 x 10^-16). Association was also detected for SNPs in two novel immune-related loci, RERE (P = 7.07 x 10^-15), GZMB (P = 3.44 x 10^-8), and in a locus that may mediate melanocyte target cell specificity, TYR (P = 1.60 x 10^-18) encoding tyrosinase. These findings thus demonstrate association between generalized vitiligo and multiple genes, some associated with other autoimmune diseases and others that may mediate target-cell specificity, and suggest a possible inverse relationship between susceptibility to vitiligo versus melanoma.