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Nat Commun. 2015 May 5;6:7001. doi: 10.1038/ncomms8001.

Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci.

Author information

  • 1Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 21] Division of Genetics and Molecular Medicine, King's College London, London WC2R 2LS, UK [2] Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • 3Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
  • 4Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • 5Division of Genetics and Molecular Medicine, King's College London, London WC2R 2LS, UK.
  • 61] Neuroscience Research, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8 [2] National Institute for Health Research (NIHR), Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust, London SE1 9RT, UK.
  • 7Department of Dermatology, University Hospital, Schleswig-Holstein, Christian-Albrechts-University, 24105 Kiel, Germany.
  • 8Department of Pathophysiology, Centre of Translational Medicine and Centre for Translational Genomics, University of Tartu, 50409 Tartu, Estonia.
  • 9Department of Dermatology and Venereology, University of Tartu, 50409 Tartu, Estonia.
  • 10Estonian Genome Center, University of Tartu, 51010 Tartu, Estonia.
  • 11Department of Dermatology, Linköping University, SE-581 83 Linköping, Sweden.
  • 12Department of Dermatology, University of Utah, Salt Lake City, Utah 84132, USA.
  • 13Department of Medicine, Division of Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada M5T 2S8.
  • 14Department of Medicine, Division of Dermatology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada M5T 2S8.
  • 15Department of Medicine, Memorial University, St John's, Newfoundland, Canada A1C 5B8.
  • 16Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen 91054, Germany.
  • 17Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AD, UK.
  • 181] Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109, USA [2] Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan 48105, USA.

Abstract

Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

PMID:
25939698
PMCID:
PMC4422106
DOI:
10.1038/ncomms8001
[PubMed - indexed for MEDLINE]
Free PMC Article
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