Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants
| Autor: | Mauro Picardo, Richard A. Spritz, Roberta Colucci, J.P. Wietze van der Veen, Iltefat H. Hamzavi, Henry W. Lim, Anthony P. Weetman, Igor V. Korobko, Ele Prans, Pamela R. Fain, Stephanie A. Santorico, Alain Taïeb, Nanja van Geel, Albert Wolkerstorfer, Khaled Ezzedine, Markus Böhm, Rosalie M. Luiten, A. Hartmann, E. Helen Kemp, Janet C. Siebert, Jo Lambert, Silvia Moretti, Genevieve H.L. Andersen, Nanette B. Silverberg, Andreas Overbeck, Qing-Sheng Mi, Tracey M. Ferrara, Külli Kingo, Songtao Ben, Daniel Yorgov, Mats Olsson, Paulene J. Holland, Maire Karelson, Yan Valle, Li Zhou, David J. Gawkrodger, Margaret R. Wallace, Ying Jin, Dorothy C. Bennett, Stanca A. Birlea, Kelly M. Brownson, Sulev Kõks, Wayne T. McCormack, Anne Lienert |
|---|---|
| Přispěvatelé: | AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, Dermatology, Other Research |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Genotype Quantitative Trait Loci Vitiligo Genome-wide association study Biology Quantitative trait locus Risk Assessment Article Autoimmune Diseases 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans Genetic Predisposition to Disease skin and connective tissue diseases Melanoma Genetic association Autoimmune disease integumentary system medicine.disease Genetic architecture 3. Good health 030104 developmental biology 030220 oncology & carcinogenesis Expression quantitative trait loci Female Imputation (genetics) Genome-Wide Association Study |
| Zdroj: | NATURE GENETICS Nature genetics, 48(11), 1418-1424. Nature Publishing Group Nature genetics |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.3680 |
| Popis: | Vitiligo is an autoimmune disease in which depigmented skin results from destruction of\ud skin melanocytes, with strong epidemiologic association with several other autoimmune\ud diseases. In previous linkage and genome-wide association studies (GWAS1, GWAS2),\ud we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We\ud carried out a third GWAS (GWAS3) of vitiligo in EUR subjects, with augmentation of\ud GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three\ud vitiligo GWAS, followed by an independent replication study. The combined analyses,\ud with 4,680 vitiligo cases and 39,586 controls, identified 23 novel replicated loci, as well as\ud 7 new suggestive loci, most encoding immune regulators, apoptotic regulators, and\ud melanocyte regulators, several of which are also associated with other autoimmune\ud diseases. Functional analyses indicate a predominance of causal regulatory variation, in\ud some cases corresponding to eQTL at these loci. Together, the identified genes provide\ud a framework for vitiligo genetic architecture and pathobiology, highlight genetic\ud relationships to other autoimmune diseases and melanoma, and offer potential targets\ud for vitiligo treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink