VitGene Generalized Vitiligo Genetics Study
Ontology highlight
ABSTRACT: 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.
PROVIDER: phs000224.v1.p1 | EGA |
REPOSITORIES: EGA
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Project description:<p>"Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10<sup>-7</sup> < P(overall) < 1.6 x 10<sup>-23</sup>; odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10<sup>-5</sup>) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10<sup>-7</sup>). Our results show that numerous genes, some with known immune-related functions, predispose to SLE." Reprinted from Nature Genetics, 2008 Feb; 40(2):204-10, PMID:<a href="http://www.ncbi.nlm.nih.gov/pubmed/18204446" target="_blank">18204446</a>, with permission from Nature Publishing Group. Data submitted to dbGaP includes 297 samples from Oklahoma. (Please see also Study Accession: <a href="./study.cgi?id=phs000216">phs000216.v1.p1</a>)</p>
| phs000202.v1.p1 | EGA
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2015-10-15 | GSE65424 | GEO
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2012-04-30 | GSE15905 | GEO
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2016-01-21 | E-GEOD-77052 | biostudies-arrayexpress
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2015-11-24 | E-GEOD-69600 | biostudies-arrayexpress
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| phs000272.v1.p1 | EGA