Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Ying Jin; Genevieve Andersen; Daniel Yorgov; Tracey M. Ferrara; Songtao Ben; Kelly M. Brownson; Paulene J. Holland; Stanca A. Birlea; Janet Siebert; Anke Hartmann; Anne Lienert; Nanja van Geel; Jo Lambert; Rosalie M. Luiten; Albert Wolkerstorfer; J. P. Wietze van der Veen; Dorothy C. Bennett; Alain Taïeb; Khaled Ezzedine; E. Helen Kemp; David J. Gawkrodger; Anthony P. Weetman; Sulev Kõks; Ele Prans; Külli Kingo; Maire Karelson; Margaret R. Wallace; Wayne T. McCormack; Andreas Overbeck; Silvia Moretti; Roberta Colucci; Mauro Picardo; Nanette B. Silverberg; Mats Olsson; Yan Valle; Igor Korobko; Markus Böhm; Henry W. Lim; Iltefat Hamzavi; Li Zhou; Qing-Sheng Mi; Pamela R. Fain; Stephanie A. Santorico; Richard A. Spritz

doi:https://doi.org/10.1038/ng.3680

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

Ying Jin, Genevieve Andersen, Daniel Yorgov, Tracey M. Ferrara, Songtao Ben, Kelly M. Brownson, Paulene J. Holland, Stanca A. Birlea, Janet Siebert, Anke Hartmann, Anne Lienert, Nanja van Geel, Jo Lambert, Rosalie M. Luiten, Albert Wolkerstorfer, J. P. Wietze van der Veen, Dorothy C. Bennett, Alain Taïeb, Khaled Ezzedine, E. Helen KempDavid J. Gawkrodger, Anthony P. Weetman, Sulev Kõks, Ele Prans, Külli Kingo, Maire Karelson, Margaret R. Wallace, Wayne T. McCormack, Andreas Overbeck, Silvia Moretti, Roberta Colucci, Mauro Picardo, Nanette B. Silverberg, Mats Olsson, Yan Valle, Igor Korobko, Markus Böhm, Henry W. Lim, Iltefat Hamzavi, Li Zhou, Qing-Sheng Mi, Pamela R. Fain, Stephanie A. Santorico, Richard A. Spritz

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment

Original language	English
Pages (from-to)	1418-1424
Journal	Nature Genetics
Volume	48
Issue number	11
DOIs	https://doi.org/10.1038/ng.3680
Publication status	Published - 2016

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https://doi.org/10.1038/ng.3680

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Jin, Y., Andersen, G., Yorgov, D., Ferrara, T. M., Ben, S., Brownson, K. M., Holland, P. J., Birlea, S. A., Siebert, J., Hartmann, A., Lienert, A., van Geel, N., Lambert, J., Luiten, R. M., Wolkerstorfer, A., Wietze van der Veen, J. P., Bennett, D. C., Taïeb, A., Ezzedine, K., ... Spritz, R. A. (2016). Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nature Genetics, 48(11), 1418-1424. https://doi.org/10.1038/ng.3680

@article{6c3a880f54a347ff865f587bc2886631,

title = "Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants",

abstract = "Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment",

author = "Ying Jin and Genevieve Andersen and Daniel Yorgov and Ferrara, {Tracey M.} and Songtao Ben and Brownson, {Kelly M.} and Holland, {Paulene J.} and Birlea, {Stanca A.} and Janet Siebert and Anke Hartmann and Anne Lienert and {van Geel}, Nanja and Jo Lambert and Luiten, {Rosalie M.} and Albert Wolkerstorfer and {Wietze van der Veen}, {J. P.} and Bennett, {Dorothy C.} and Alain Ta{\"i}eb and Khaled Ezzedine and Kemp, {E. Helen} and Gawkrodger, {David J.} and Weetman, {Anthony P.} and Sulev K{\~o}ks and Ele Prans and K{\"u}lli Kingo and Maire Karelson and Wallace, {Margaret R.} and McCormack, {Wayne T.} and Andreas Overbeck and Silvia Moretti and Roberta Colucci and Mauro Picardo and Silverberg, {Nanette B.} and Mats Olsson and Yan Valle and Igor Korobko and Markus B{\"o}hm and Lim, {Henry W.} and Iltefat Hamzavi and Li Zhou and Qing-Sheng Mi and Fain, {Pamela R.} and Santorico, {Stephanie A.} and Spritz, {Richard A.}",

year = "2016",

doi = "https://doi.org/10.1038/ng.3680",

language = "English",

volume = "48",

pages = "1418--1424",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

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Jin, Y, Andersen, G, Yorgov, D, Ferrara, TM, Ben, S, Brownson, KM, Holland, PJ, Birlea, SA, Siebert, J, Hartmann, A, Lienert, A, van Geel, N, Lambert, J, Luiten, RM , Wolkerstorfer, A, Wietze van der Veen, JP, Bennett, DC, Taïeb, A, Ezzedine, K, Kemp, EH, Gawkrodger, DJ, Weetman, AP, Kõks, S, Prans, E, Kingo, K, Karelson, M, Wallace, MR, McCormack, WT, Overbeck, A, Moretti, S, Colucci, R, Picardo, M, Silverberg, NB, Olsson, M, Valle, Y, Korobko, I, Böhm, M, Lim, HW, Hamzavi, I, Zhou, L, Mi, Q-S, Fain, PR, Santorico, SA & Spritz, RA 2016, 'Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants', Nature Genetics, vol. 48, no. 11, pp. 1418-1424. https://doi.org/10.1038/ng.3680

TY - JOUR

T1 - Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

AU - Jin, Ying

AU - Andersen, Genevieve

AU - Yorgov, Daniel

AU - Ferrara, Tracey M.

AU - Ben, Songtao

AU - Brownson, Kelly M.

AU - Holland, Paulene J.

AU - Birlea, Stanca A.

AU - Siebert, Janet

AU - Hartmann, Anke

AU - Lienert, Anne

AU - van Geel, Nanja

AU - Lambert, Jo

AU - Luiten, Rosalie M.

AU - Wolkerstorfer, Albert

AU - Wietze van der Veen, J. P.

AU - Bennett, Dorothy C.

AU - Taïeb, Alain

AU - Ezzedine, Khaled

AU - Kemp, E. Helen

AU - Gawkrodger, David J.

AU - Weetman, Anthony P.

AU - Kõks, Sulev

AU - Prans, Ele

AU - Kingo, Külli

AU - Karelson, Maire

AU - Wallace, Margaret R.

AU - McCormack, Wayne T.

AU - Overbeck, Andreas

AU - Moretti, Silvia

AU - Colucci, Roberta

AU - Picardo, Mauro

AU - Silverberg, Nanette B.

AU - Olsson, Mats

AU - Valle, Yan

AU - Korobko, Igor

AU - Böhm, Markus

AU - Lim, Henry W.

AU - Hamzavi, Iltefat

AU - Zhou, Li

AU - Mi, Qing-Sheng

AU - Fain, Pamela R.

AU - Santorico, Stephanie A.

AU - Spritz, Richard A.

PY - 2016

Y1 - 2016

N2 - Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment

AB - Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment

U2 - https://doi.org/10.1038/ng.3680

DO - https://doi.org/10.1038/ng.3680

M3 - Article

C2 - 27723757

SN - 1061-4036

VL - 48

SP - 1418

EP - 1424

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -