Please use this identifier to cite or link to this item:
Title: Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
Author: Carmona, F. David
Coit, Patrick
Saruhan Direskeneli, Güher
Hernández Rodríguez, José
Cid Xutglà, M. Cinta
Solans, Roser
Castañeda, Santos
Vaglio, Augusto
Direskeneli, Haner
Merkel, Peter A.
Boiardi, Luigi
Salvarani, Carlo
González-Gay, Miguel A.
Martín, Javier
Sawalha, Amr H.
Spanish GCA Study Group
Narváez García, Francisco Javier
Italian GCA Study Group
Turkish Takayasu Study Group
Vasculitis Clinical Research Consortium
Keywords: Genòmica
Issue Date: 9-Mar-2017
Publisher: Nature Publishing Group
Abstract: Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.
Note: Reproducció del document publicat a:
It is part of: Scientific Reports, 2017, vol. 7, num. 43953
Related resource:
ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)

Files in This Item:
File Description SizeFormat 
670306.pdf1.12 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons