Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants.

Nat Commun
Authors
Abstract

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 >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 NFκB 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 T0, T1 and T17). The identified loci explain ∼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 × 10). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

Year of Publication
2017
Journal
Nat Commun
Volume
8
Pages
15382
Date Published
2017 May 24
ISSN
2041-1723
DOI
10.1038/ncomms15382
PubMed ID
28537254
PubMed Central ID
PMC5458077
Links
Grant list
K08 AR060802 / AR / NIAMS NIH HHS / United States
R01 AR042742 / AR / NIAMS NIH HHS / United States
R01 AR054966 / AR / NIAMS NIH HHS / United States
R01 AR050511 / AR / NIAMS NIH HHS / United States
R01 AR065183 / AR / NIAMS NIH HHS / United States
R01 AR063611 / AR / NIAMS NIH HHS / United States
Wellcome Trust / United Kingdom
R44 HG006981 / HG / NHGRI NIH HHS / United States
MR/L011808/1 / Medical Research Council / United Kingdom