Ortiz-Fernandez, LourdesCarmona, Francisco DavidLopez-Mejias, RaquelGonzalez-Escribano, Maria FranciscaLyons, Paul AMorgan, Ann WSawalha, Amr HMerkel, Peter ASmith, Kenneth G CGonzalez-Gay, Miguel AMartin, Javier2023-01-252023-01-252018-01-27Ortiz-Fernández L, Carmona FD, López-Mejías R, González-Escribano MF, Lyons PA, Morgan AW, et al. Cross-phenotype analysis of Immunochip data identifies KDM4C as a relevant locus for the development of systemic vasculitis. Ann Rheum Dis. 2018 Apr;77(4):589-595.http://hdl.handle.net/10668/12055Systemic vasculitides represent a heterogeneous group of rare complex diseases of the blood vessels with a poorly understood aetiology. To investigate the shared genetic component underlying their predisposition, we performed the first cross-phenotype meta-analysis of genetic data from different clinically distinct patterns of vasculitis. Immunochip genotyping data from 2465 patients diagnosed with giant cell arteritis, Takayasu's arteritis, antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as well as 4632 unaffected controls were analysed to identify common susceptibility loci for vasculitis development. The possible functional consequences of the associated variants were interrogated using publicly available annotation data. The strongest association signal corresponded with an intergenic polymorphism located between HLA-DQB1 and HLA-DQA2 (rs6932517, P=4.16E-14, OR=0.74). This single nucleotide polymorphism is in moderate linkage disequilibrium with the disease-specific human leucocyte antigen (HLA) class II associations of each type of vasculitis and could mark them. Outside the HLA region, we identified the KDM4C gene as a common risk locus for vasculitides (highest peak rs16925200, P=6.23E-07, OR=1.75). This gene encodes a histone demethylase involved in the epigenetic control of gene expression. Through a combined analysis of Immunochip data, we have identified KDM4C as a new risk gene shared between systemic vasculitides, consistent with the increasing evidences of the crucial role that the epigenetic mechanisms have in the development of complex immune-mediated conditions.enautoantibodiesoutcomes researchsystemic sclerosisAnti-Neutrophil Cytoplasmic Antibody-Associated VasculitisCase-Control StudiesEpigenesis, GeneticFemaleGenetic LociGenetic Predisposition to DiseaseGiant Cell ArteritisHLA-DQ AntigensHLA-DQ beta-ChainsHumansJumonji Domain-Containing Histone DemethylasesLinkage DisequilibriumMalePhenotypePolymorphism, Single NucleotideProtein Array AnalysisSystemic VasculitisTakayasu Arteritisresearch article29374629Restricted AccessVasculitisEpigenómicaVasculitis sistémicaPolimorfismo de nucleótido simpleFenotipoVasculitis por IgAAnticuerpos anticitoplasma de neutrófilosHistona DemetilasasArteritis de Takayasu10.1136/annrheumdis-2017-2123721468-2060PMC5849568https://europepmc.org/articles/pmc5849568?pdf=renderhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849568/pdf