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

Author

Listed:
  • Xianyong Yin

    (Anhui Medical University
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, 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
    Melvin and Bren Simon Cancer Center, Indiana University
    School of Medicine, Indiana University)

  • Xavier Estivill

    (Genetic Causes of Disease Group, Centre for Genomic Regulation (CRG)
    Universitat Pompeu Fabra, Barcelona
    Hospital del Mar Medical Research Institute (IMIM), Barcelona
    CIBER in Epidemiology and Public Health (CIBERESP), Barcelona)

  • Liangdan Sun

    (Anhui Medical University
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University)

  • Xianbo Zuo

    (Anhui Medical University
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University)

  • Changbing Shen

    (Anhui Medical University
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University)

  • Caihong Zhu

    (Anhui Medical University
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University)

  • Anping Zhang

    (Anhui Medical University
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, 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
    National University of Singapore, Singapore 138672, 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
    Program in Translational NeuroPsychiatric Genomics, Brigham & Women’s Hospital, Harvard Medical School)

  • Abrar A. Qureshi

    (Richard M. Fairbanks School of Public Health, Indiana University
    Melvin and Bren Simon Cancer Center, Indiana University
    Program in Translational NeuroPsychiatric Genomics, Brigham & Women’s Hospital, Harvard Medical School)

  • Paul I. W. de Bakker

    (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht
    Center for Molecular Medicine, University Medical Center Utrecht)

  • Mark Seielstad

    (Genome Institute of Singapore, A*STAR
    Institute for Human Genetics, University of California San Francisco)

  • 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
    State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University)

  • Jianjun Liu

    (State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University
    Key Lab of Dermatology (Anhui Medical University), Ministry of Education
    Collaborative Innovation Center for Complex and Severe Skin Diseases, Anhui Medical University
    Genome Institute of Singapore, A*STAR)

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.

Suggested Citation

  • 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 Pa, 2015. "Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7916
    DOI: 10.1038/ncomms7916
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    Cited by:

    1. Qian Xiao & Joseph Mears & Aparna Nathan & Kazuyoshi Ishigaki & Yuriy Baglaenko & Noha Lim & Laura A. Cooney & Kristina M. Harris & Mark S. Anderson & David A. Fox & Dawn E. Smilek & James G. Krueger , 2023. "Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Yuanqiang Sun & Wenchao Li & Zhenzhen Wang & Yongliang Yang & Ziyang Zhang & Gongqi Yu & Chuan Wang & Xu Sang & Yingjie Lin & Guangliang Zhang & Haixia Wang & Yilei Wu & Jianwen Wang & Fuxiang Bai & J, 2026. "Genome-wide pQTL mapping in human skin identifies specific genetic regulators and mechanistic links to skin disorders," Nature Communications, Nature, vol. 17(1), pages 1-25, December.
    3. Ruolin Li & Wenjin Luo & Xiangjun Chen & Qinglian Zeng & Shumin Yang & Ping Wang & Jinbo Hu & Aijun Chen, 2024. "An observational and genetic investigation into the association between psoriasis and risk of malignancy," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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