Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy

Francisco David Carmona, Patrick Coit, Güher Saruhan-Direskeneli, José Hernández-Rodríguez, María C. Cid, Roser Solans, Santos Castañeda, Augusto Vaglio, Haner Direskeneli, Peter A. Merkel, Luigi Boiardi, Carlo Salvarani, Miguel A. González-Gay, Javier Martín, Amr H. Sawalha

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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; OR GCA = 1.19, OR TAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P GCA = 5.52E-04, OR GCA = 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.

Original languageEnglish
Article number43953
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Mar 9 2017

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Giant Cell Arteritis
Vasculitis
Takayasu Arteritis
Meta-Analysis
Genetic Pleiotropy
MHC Class I Genes
HLA-DRB1 Chains
MHC Class II Genes
HLA-B Antigens

ASJC Scopus subject areas

  • General

Cite this

Carmona, F. D., Coit, P., Saruhan-Direskeneli, G., Hernández-Rodríguez, J., Cid, M. C., Solans, R., ... Sawalha, A. H. (2017). Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy. Scientific Reports, 7, [43953]. https://doi.org/10.1038/srep43953

Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy. / Carmona, Francisco David; Coit, Patrick; Saruhan-Direskeneli, Güher; Hernández-Rodríguez, José; Cid, María C.; Solans, Roser; Castañeda, Santos; Vaglio, Augusto; Direskeneli, Haner; Merkel, Peter A.; Boiardi, Luigi; Salvarani, Carlo; González-Gay, Miguel A.; Martín, Javier; Sawalha, Amr H.

In: Scientific Reports, Vol. 7, 43953, 09.03.2017.

Research output: Contribution to journalArticle

Carmona, FD, Coit, P, Saruhan-Direskeneli, G, Hernández-Rodríguez, J, Cid, MC, Solans, R, Castañeda, S, Vaglio, A, Direskeneli, H, Merkel, PA, Boiardi, L, Salvarani, C, González-Gay, MA, Martín, J & Sawalha, AH 2017, 'Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy', Scientific Reports, vol. 7, 43953. https://doi.org/10.1038/srep43953
Carmona FD, Coit P, Saruhan-Direskeneli G, Hernández-Rodríguez J, Cid MC, Solans R et al. Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy. Scientific Reports. 2017 Mar 9;7. 43953. https://doi.org/10.1038/srep43953
Carmona, Francisco David ; Coit, Patrick ; Saruhan-Direskeneli, Güher ; Hernández-Rodríguez, José ; Cid, María C. ; Solans, Roser ; Castañeda, Santos ; Vaglio, Augusto ; Direskeneli, Haner ; Merkel, Peter A. ; Boiardi, Luigi ; Salvarani, Carlo ; González-Gay, Miguel A. ; Martín, Javier ; Sawalha, Amr H. / Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy. In: Scientific Reports. 2017 ; Vol. 7.
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