Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility
Year: 2015
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms7916
Authors: 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
Institutions: Anhui Medical University, Agency for Science, Technology and Research, Genome Institute of Singapore, Christian-Albrechts-Universität zu Kiel, Indiana University Indianapolis, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Universitat Pompeu Fabra, Hospital Del Mar, Centre for Genomic Regulation, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Hospital del Mar Research Institute, Karolinska Institutet, University of Utah, University Hospital Schleswig-Holstein, National University of Singapore, National Skin Centre, University of California, San Francisco, Imperial College London, Broad Institute, Brigham and Women's Hospital, Harvard University, University Medical Center Utrecht, National University Health System
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Psoriasis Foundation, Psoriasis Association, Multiple Sclerosis Society, Agency for Science, Technology and Research, Deutsche Forschungsgemeinschaft, National Natural Science Foundation of China, Bundesministerium für Bildung und Forschung, Generalitat de Catalunya, Anhui Medical University, Karolinska Institutet, Exzellenzclusters Entzündungsforschung, National Institutes of Health, Brigham Research Institute, National Outstanding Youth Science Fund Project of National Natural Science Foundation of China, Medical Research Council, Agència de Gestió d'Ajuts Universitaris i de Recerca, National Key Research and Development Program of China, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1009429141, G1189944011, G122132715, G2058425106, G3277580850, G3483617671, IL-23/Th17通路基因及其交互作用与银屑病易感性研究, G4125319534, G4267133268, Verbundprojekt sysINFLAME: Netzwerk für Systemmedizin chronisch-entzündlicher Erkrankungen, CP1a, 2, 3, 4 , 5, 7, 8, 9b, 10b, AP, Genetic Analysis of the TNF Pathway in Psoriasis, G6310597225, Identification of Causal Variants in Psoriasis, G6929123101, G7086254578, G778448485, Genome-Wide SNP Association in Psoriasis, G7990331346, G8330332523, G8675107807, G8721160492, G8797496111, G8855648219, Zentrale Biomaterialbank der Universität Kiel: Das popgen 2.0-Netzwerk, G985971609, G989722597
OpenAlex ID: W1993249218