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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/49560

Title: A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis
Authors: López-Mejías, Raquel
Carmona López, Francisco David
Castañeda, Santos
Genre, Fernanda
Remuzgo-Martínez, Sara
Sevilla-Pérez, Belén
Ortego-Centeno, Norberto
Llorca, Javier
Ubilla, Begoña
Mijares, Verónica
Pina, Trinitario
Miranda-Filloy, José A.
Navas Parejo, Antonio
Argila, Diego de
Aragües, Maximiliano
Rubio, Esteban
León Luque, Manuel
Blanco-Madrigal, Juan María
Galíndez-Aguirregoikoa, Eva
Jayne, David
Blanco, Ricardo
Martín, Javier
González-Gay, Miguel A.
Issue Date: 11-Jul-2017
Abstract: The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46–0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease.
Sponsorship: This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI12/00193) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). RL-M was supported by the Miguel Servet I programme of the Spanish Ministry of Economy and Competitiveness through the grant CP16/00033. FDC was supported by the Ramón y Cajal programme of the Spanish Ministry of Economy and Competitiveness through the grant RYC-2014-16458. FG was recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD15/00095). SR-M and BU were supported by funds from the RETICS Program (RIER) (RD16/0012/0009 and RD12/0009/0013, respectively).
Publisher: Nature
Keywords: Vasculitis
Genome-wide association study (GWAS)
Human leukocyte antigen (HLA)
Henoch-Schonlein purpura
URI: http://hdl.handle.net/10481/49560
ISSN: 2045-2322
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: López-Mejías, R.; et al. A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis. Scientific Reports, 7: 5088 (2017). [http://hdl.handle.net/10481/49560]
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