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

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms7916

2041-1723

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 Sánchez, Leonid Padyukov, Joseph J. Catanese, Gerald G. Krueger, Kristina Callis Duffin, Sören Mucha, Michael Weichenthal, Stephan Weidinger, Wolfgang Lieb, Jia Nee Foo, Yi Li, Kar Seng Sim, Herty Liany, Ishak D. Irwan, Yik‐Ying Teo, Colin Theng, Rashmi Gupta, A. Bowcock, Philip L. De Jager, Abrar A. Qureshi, Paul I. W. de Bakker, Mark Seielstad, Wilson Liao, Mona Ståhle, André Franke, Xuejun Zhang, Jianjun Liu,

Dermatology and Skin Diseases

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.