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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 Vasculitis Genomics Vasculitis |
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: https://doi.org/10.1038/srep43953 |
It is part of: | Scientific Reports, 2017, vol. 7, num. 43953 |
URI: | http://hdl.handle.net/2445/120343 |
Related resource: | https://doi.org/10.1038/srep43953 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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