Dataset Information

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

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 NF?B 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 TH0, TH1 and TH17). 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 × 10-89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

SUBMITTER: Tsoi LC

PROVIDER: S-EPMC5458077 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Tsoi Lam C LC Stuart Philip E PE Tian Chao C Gudjonsson Johann E JE Das Sayantan S Zawistowski Matthew M Ellinghaus Eva E Barker Jonathan N JN Chandran Vinod V Dand Nick N Duffin Kristina Callis KC Enerbäck Charlotta C Esko Tõnu T Franke Andre A Gladman Dafna D DD Hoffmann Per P Kingo Külli K Kõks Sulev S Krueger Gerald G GG Lim Henry W HW Metspalu Andres A Mrowietz Ulrich U Mucha Sören S Rahman Proton P Reis Andre A Reis Andre A Tejasvi Trilokraj T Trembath Richard R Voorhees John J JJ Weidinger Stephan S Weichenthal Michael M Wen Xiaoquan X Eriksson Nicholas N Kang Hyun M HM Hinds David A DA Nair Rajan P RP Abecasis Gonçalo R GR Elder James T JT

Nature communications 20170524

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 ro ...[more]

PMID: 28537254

Similar Datasets

Project description:Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comprehensive view of PCOS that encompasses multiple diagnostic criteria, gender, reproductive potential and mental health.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets