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 () and Jianjun Liu ()
Additional contact information
Xianyong Yin: Anhui Medical University
Hui Qi Low: Genome Institute of Singapore, A*STAR
Ling Wang: Genome Institute of Singapore, A*STAR
Yonghong Li: Celera
Eva Ellinghaus: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
Jiali Han: Richard M. Fairbanks School of Public Health, Indiana University
Xavier Estivill: Genetic Causes of Disease Group, Centre for Genomic Regulation (CRG)
Liangdan Sun: Anhui Medical University
Xianbo Zuo: Anhui Medical University
Changbing Shen: Anhui Medical University
Caihong Zhu: Anhui Medical University
Anping Zhang: Anhui Medical University
Fabio Sanchez: Unit of Dermatology and Venereology, Karolinska Institutet
Leonid Padyukov: Rheumatology Unit, Karolinska Institutet
Joseph J. Catanese: Celera
Gerald G. Krueger: University of Utah
Kristina Callis Duffin: University of Utah
Sören Mucha: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
Michael Weichenthal: University Hospital Schleswig-Holstein, Christian-Albrechts-University
Stephan Weidinger: University Hospital Schleswig-Holstein, Christian-Albrechts-University
Wolfgang Lieb: Institute of Epidemiology and Biobank PopGen, Christian Albrechts University
Jia Nee Foo: Genome Institute of Singapore, A*STAR
Yi Li: Genome Institute of Singapore, A*STAR
Karseng Sim: Genome Institute of Singapore, A*STAR
Herty Liany: Genome Institute of Singapore, A*STAR
Ishak Irwan: Genome Institute of Singapore, A*STAR
Yikying Teo: National University of Singapore
Colin T. S. Theng: National Skin Centre
Rashmi Gupta: University of California San Francisco
Anne Bowcock: National Heart and Lung Institute, Imperial College
Philip L. De Jager: Program in Medical and Population Genetics, Broad Institute
Abrar A. Qureshi: Richard M. Fairbanks School of Public Health, Indiana University
Paul I. W. de Bakker: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht
Mark Seielstad: Genome Institute of Singapore, A*STAR
Wilson Liao: University of California San Francisco
Mona Ståhle: Unit of Dermatology and Venereology, Karolinska Institutet
Andre Franke: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
Xuejun Zhang: Anhui Medical University
Jianjun Liu: State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7916

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