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Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants
University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA; University of Michigan, MI 48109 USA.
University of Michigan, MI 48109 USA.
23andMe Inc, CA 94041 USA.
University of Michigan, MI 48109 USA.
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, 15382Article in journal (Refereed) Published
Abstract [en]

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size amp;gt;39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFkB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including T(H)0, T(H)1 and T(H)17). The identified loci explain similar to 28% of the genetic heritability and generate a discriminatory genetic risk score (AUC = 0.76 in our sample) that is significantly correlated with age at onset (p = 2 x 10(-89)). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 8, 15382
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:liu:diva-138240DOI: 10.1038/ncomms15382ISI: 000401959400001PubMedID: 28537254OAI: oai:DiVA.org:liu-138240DiVA: diva2:1109386
Note

Funding Agencies|National Institutes of Health [R01AR042742, R01AR050511, R01AR054966, R01AR063611, R01AR065183]; Foundation for the National Institutes of Health; Dermatology Foundation; National Psoriasis Foundation; Arthritis National Research Foundation; Ann Arbor Veterans Affairs Hospital; Dawn and Dudley Holmes Foundation; Babcock Memorial Trust; Medical Research Council [MR/L011808/1]; German Ministry of Education and Research (BMBF); Doris Duke Foundation [2013106]; National Institute of Health [K08AR060802, R01AR06907]; Taubman Medical Research Institute; Department of Health via the NIHR comprehensive Biomedical Research Center; Kings College London; KCH NHS Foundation Trust; Barbara and Neal Henschel Charitable Foundation; 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); National Human Genome Research Institute of the National Institutes of Health [R44HG006981]; International Psoriasis Council

Available from: 2017-06-14 Created: 2017-06-14 Last updated: 2017-07-03

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