title: Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy.
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.
authors.affiliation: Instituto de Parasitología y Biomedicina 'López-Neyra', IPBLN-CSIC, PTS Granada, Granada, Spain.|Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, Granada 18016, Spain.
authors.forename: F David
authors.initials: FD
authors.lastname: Carmona
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Coit
authors.affiliation: Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Güher
authors.initials: G
authors.lastname: Saruhan-Direskeneli
authors.affiliation: Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Hernández-Rodríguez
authors.affiliation: Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Cid
authors.affiliation: Autoimmune Systemic Diseases Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Solans
authors.affiliation: Department of Rheumatology, Hospital de la Princesa, IIS-IP, Madrid, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Unit of Nephrology, University Hospital of Parma, Parma, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.affiliation: Marmara University, School of Medicine, Department of Rheumatology, Istanbul, Turkey.
authors.forename: Haner
authors.initials: H
authors.lastname: Direskeneli
authors.affiliation: Division of Rheumatology and Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.affiliation: Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Boiardi
authors.affiliation: Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Salvarani
authors.affiliation: Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Santander, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.affiliation: Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, Granada 18016, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D013700:Giant Cell Arteritis / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D013625:Takayasu Arteritis / Q000235:genetics*
chemical_list: D006680:HLA Antigens