Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

Xianyong Yin; Hui Qi Low; Ling Wang; Yonghong Li; Eva Ellinghaus; Jiali Han; Xavier Estivill; Liangdan Sun; Xianbo Zuo; Changbing Shen; Caihong Zhu; Anping Zhang; Fabio Sanchez; Leonid Padyukov; Joseph J. Catanese; Gerald G. Krueger; Kristina Callis Duffin; Sören Mucha; Michael Weichenthal; Stephan Weidinger; Wolfgang Lieb; Jia Nee Foo; Yi Li; Karseng Sim; Herty Liany; Ishak Irwan; Yikying Teo; Colin T.S. Theng; Rashmi Gupta; Anne Bowcock; Philip L. De Jager; Abrar A. Qureshi; Paul I.W. De Bakker; Mark Seielstad; Wilson Liao; Mona Ståhle; Andre Franke; Xuejun Zhang; Jianjun Liu

doi:10.1038/ncomms7916

Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

Xianyong Yin, Hui Qi Low, Ling Wang, Yonghong Li, Eva Ellinghaus, Jiali Han, Xavier Estivill, Liangdan Sun, Xianbo Zuo, Changbing Shen, Caihong Zhu, Anping Zhang, Fabio Sanchez, Leonid Padyukov, Joseph J. Catanese, Gerald G. Krueger, Kristina Callis Duffin, Sören Mucha, Michael Weichenthal, Stephan WeidingerWolfgang Lieb, Jia Nee Foo, Yi Li, Karseng Sim, Herty Liany, Ishak Irwan, Yikying Teo, Colin T.S. Theng, Rashmi Gupta, Anne Bowcock, Philip L. De Jager, Abrar A. Qureshi, Paul I.W. De Bakker, Mark Seielstad, Wilson Liao, Mona Ståhle, Andre Franke^*, Xuejun Zhang, Jianjun Liu

^*Corresponding author for this work

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

163 Citations (Scopus)

Abstract

Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

Original language	English
Article number	6916
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7916
Publication status	Published - Apr 23 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Yin, X., Low, H. Q., Wang, L., Li, Y., Ellinghaus, E., Han, J., Estivill, X., Sun, L., Zuo, X., Shen, C., Zhu, C., Zhang, A., Sanchez, F., Padyukov, L., Catanese, J. J., Krueger, G. G., Duffin, K. C., Mucha, S., Weichenthal, M., ... Liu, J. (2015). Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. Nature Communications, 6, Article 6916. https://doi.org/10.1038/ncomms7916

@article{27e43d00b8f9407ebf388bd689dbab3b,

title = "Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility",

abstract = "Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.",

author = "Xianyong Yin and Low, {Hui Qi} and Ling Wang and Yonghong Li and Eva Ellinghaus and Jiali Han and Xavier Estivill and Liangdan Sun and Xianbo Zuo and Changbing Shen and Caihong Zhu and Anping Zhang and Fabio Sanchez and Leonid Padyukov and Catanese, {Joseph J.} and Krueger, {Gerald G.} and Duffin, {Kristina Callis} and S{\"o}ren Mucha and Michael Weichenthal and Stephan Weidinger and Wolfgang Lieb and Foo, {Jia Nee} and Yi Li and Karseng Sim and Herty Liany and Ishak Irwan and Yikying Teo and Theng, {Colin T.S.} and Rashmi Gupta and Anne Bowcock and {De Jager}, {Philip L.} and Qureshi, {Abrar A.} and {De Bakker}, {Paul I.W.} and Mark Seielstad and Wilson Liao and Mona St{\aa}hle and Andre Franke and Xuejun Zhang and Jianjun Liu",

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day = "23",

doi = "10.1038/ncomms7916",

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Yin, X, Low, HQ, Wang, L, Li, Y, Ellinghaus, E, Han, J, Estivill, X, Sun, L, Zuo, X, Shen, C, Zhu, C, Zhang, A, Sanchez, F, Padyukov, L, Catanese, JJ, Krueger, GG, Duffin, KC, Mucha, S, Weichenthal, M, Weidinger, S, Lieb, W, Foo, JN, Li, Y, Sim, K, Liany, H, Irwan, I, Teo, Y, Theng, CTS, Gupta, R, Bowcock, A, De Jager, PL, Qureshi, AA, De Bakker, PIW, Seielstad, M, Liao, W, Ståhle, M, Franke, A, Zhang, X & Liu, J 2015, 'Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility', Nature Communications, vol. 6, 6916. https://doi.org/10.1038/ncomms7916

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AU - Yin, Xianyong

AU - Low, Hui Qi

AU - Wang, Ling

AU - Li, Yonghong

AU - Ellinghaus, Eva

AU - Han, Jiali

AU - Estivill, Xavier

AU - Sun, Liangdan

AU - Zuo, Xianbo

AU - Shen, Changbing

AU - Zhu, Caihong

AU - Zhang, Anping

AU - Sanchez, Fabio

AU - Padyukov, Leonid

AU - Catanese, Joseph J.

AU - Krueger, Gerald G.

AU - Duffin, Kristina Callis

AU - Mucha, Sören

AU - Weichenthal, Michael

AU - Weidinger, Stephan

AU - Lieb, Wolfgang

AU - Foo, Jia Nee

AU - Li, Yi

AU - Sim, Karseng

AU - Liany, Herty

AU - Irwan, Ishak

AU - Teo, Yikying

AU - Theng, Colin T.S.

AU - Gupta, Rashmi

AU - Bowcock, Anne

AU - De Jager, Philip L.

AU - Qureshi, Abrar A.

AU - De Bakker, Paul I.W.

AU - Seielstad, Mark

AU - Liao, Wilson

AU - Ståhle, Mona

AU - Franke, Andre

AU - Zhang, Xuejun

AU - Liu, Jianjun

PY - 2015/4/23

Y1 - 2015/4/23

N2 - Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

AB - Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

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JO - Nature Communications

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Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

Abstract

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