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

Nat Commun. 2015 Apr 23:6:6916. doi: 10.1038/ncomms7916.

Authors

Xianyong Yin¹, Hui Qi Low², Ling Wang², Yonghong Li³, Eva Ellinghaus⁴, Jiali Han⁵, Xavier Estivill⁶, Liangdan Sun¹, Xianbo Zuo¹, Changbing Shen¹, Caihong Zhu¹, Anping Zhang¹, Fabio Sanchez⁷, Leonid Padyukov⁸, Joseph J Catanese³, Gerald G Krueger⁹, Kristina Callis Duffin⁹, Sören Mucha⁴, Michael Weichenthal¹⁰, Stephan Weidinger¹⁰, Wolfgang Lieb¹¹, Jia Nee Foo², Yi Li², Karseng Sim², Herty Liany², Ishak Irwan², Yikying Teo¹², Colin T S Theng¹³, Rashmi Gupta¹⁴, Anne Bowcock¹⁵, Philip L De Jager¹⁶, Abrar A Qureshi¹⁷, Paul I W de Bakker¹⁸, Mark Seielstad¹⁹, Wilson Liao¹⁴, Mona Ståhle⁷, Andre Franke⁴, Xuejun Zhang¹, Jianjun Liu²⁰

Affiliations

¹ 1] Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [4] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China.
² Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
³ Celera, Alameda, California 94502, USA.
⁴ Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelm Street 12, Kiel 24105, Germany.
⁵ 1] Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana 46202, USA [2] Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA [3] Department of Dermatology, School of Medicine, Indiana University, Indianapolis, Indiana 46202, USA.
⁶ 1] Genetic Causes of Disease Group, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, E-08003, Spain [2] Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Catalonia, E-08003, Spain [3] Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, E-08003, Spain [4] CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Catalonia, E-08003, Spain.
⁷ Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
⁸ Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm 17177, Sweden.
⁹ Department of Dermatology, University of Utah, Salt Lake, Utah 84132, USA.
¹⁰ Department of Dermatology, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel, Germany.
¹¹ Institute of Epidemiology and Biobank PopGen, Christian Albrechts University, Kiel, Germany.
¹² 1] Departments of Statistics and Applied Probability, National University of Singapore, Singapore 138672, Singapore [2] Department of Epidemiology and Public Health, National University of Singapore, Singapore 138672, Singapore.
¹³ National Skin Centre, Singapore 308205, Singapore.
¹⁴ Department of Dermatology, University of California San Francisco, San Francisco, California 94115, USA.
¹⁵ National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
¹⁶ 1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02138, USA [2] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham &Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
¹⁷ 1] Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana 46202, USA [2] Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA [3] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham &Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
¹⁸ 1] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands [2] Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
¹⁹ 1] Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore [2] Institute for Human Genetics, University of California San Francisco, San Francisco, California 94143, USA.
²⁰ 1] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, Anhui 230032, China [2] Key Lab of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230032, China [3] Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University, Hefei, Anhui 230032, China [4] Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore [5] Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore, 138672, Singapore [6] School of Life Sciences, Anhui Medical University, Hefei, Anhui 230032, China.

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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adaptor Proteins, Vesicular Transport / genetics
Asian People / genetics*
Case-Control Studies
Core Binding Factor Alpha 2 Subunit / genetics
DEAD-box RNA Helicases / genetics
Genes, MHC Class I / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Interferon-Induced Helicase, IFIH1
Interleukin-12 Subunit p40 / genetics
Psoriasis / genetics*
Transcription Factors / genetics
Tumor Suppressor Proteins / genetics
White People / genetics*

Substances

Adaptor Proteins, Vesicular Transport
COG6 protein, human
Core Binding Factor Alpha 2 Subunit
IL12B protein, human
Interleukin-12 Subunit p40
RUNX1 protein, human
TP63 protein, human
Transcription Factors
Tumor Suppressor Proteins
IFIH1 protein, human
DEAD-box RNA Helicases
Interferon-Induced Helicase, IFIH1

Abstract

Publication types

MeSH terms

Substances

Grants and funding