Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility lociKings Coll London, England.
Centre Addict and Mental Heatlh, Canada; Guys and St Thomas NHS Fdn Trust, England.
University of Michigan, MI 48109 USA.
University of Michigan, MI 48109 USA.
Kings Coll London, England.
University of Michigan, MI 48109 USA.
University of Michigan, MI 48109 USA.
University of Kiel, Germany.
University of Michigan, MI 48109 USA.
University of Tartu, Estonia; University of Tartu, Estonia.
University of Tartu, Estonia.
University of Tartu, Estonia.
University of Michigan, MI 48109 USA.
University of Tartu, Estonia.
University of Kiel, Germany.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
University of Utah, UT 84132 USA.
University of Michigan, MI 48109 USA.
University of Toronto, Canada.
University of Toronto, Canada.
Mem University, Canada.
University of Toronto, Canada.
University of Erlangen Nurnberg, Germany.
University of Michigan, MI 48109 USA.
University of Kiel, Germany.
Kings Coll London, England.
University of Michigan, MI 48109 USA.
Queen Mary University of London, England.
University of Michigan, MI 48109 USA; Ann Arbor Vet Affairs Hospital, MI 48105 USA.
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2015 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 6, no 7001Article in journal (Refereed) Published
Abstract [en]
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 (Pless than5 x 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.
Place, publisher, year, edition, pages
Nature Publishing Group: Nature Communications , 2015. Vol. 6, no 7001
National Category
Dermatology and Venereal Diseases
Identifiers
URN: urn:nbn:se:liu:diva-119808DOI: 10.1038/ncomms8001ISI: 000355529100004PubMedID: 25939698OAI: oai:DiVA.org:liu-119808DiVA, id: diva2:827182
Note
Funding Agencies|National Institutes of Health [R01AR042742, R01AR050511, R01AR054966, R01AR062382, R01AR065183]; Wellcome Trust; German Research Foundation; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; Medical Research Council Stratified Medicine award [MR/L011808/1]; German Ministry of Education and Research (BMBF) through the e:Med sysINFLAME grant; Doris Duke Foundation; Department of Health via the NIHR comprehensive Biomedical Research Center award; Kings College London; KCH NHS Foundation Trust; Heinz Nixdorf Foundation; Estonian Ministry of Education and Research [IUT20-46]; Centre of Translational Genomics of University of Tartu (SP1GVARENG); European Regional Development Fund (Centre of Translational Medicine, University of Tartu); German Federal Ministry of Education and Research (BMBF); Ann Arbor Veterans Affairs Hospital
2015-06-262015-06-262023-03-28