A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk

• Published in: Annals of the rheumatic diseases Vol. 74; no. 10; pp. 1875 - 1881
• Main Authors: Julià, Antonio, Pinto, José Antonio, Gratacós, Jordi, Queiró, Rubén, Ferrándiz, Carlos, Fonseca, Eduardo, Montilla, Carlos, Torre-Alonso, Juan Carlos, Puig, Lluís, Pérez Venegas, José Javier, Fernández Nebro, Antonio, Fernández, Emilia, Muñoz-Fernández, Santiago, Daudén, Esteban, González, Carlos, Roig, Daniel, Sánchez Carazo, José Luís, Zarco, Pedro, Erra, Alba, López Estebaranz, José Luís, Rodríguez, Jesús, Ramírez, David Moreno, de la Cueva, Pablo, Vanaclocha, Francisco, Herrera, Enrique, Castañeda, Santos, Rubio, Esteban, Salvador, Georgina, Díaz-Torné, César, Blanco, Ricardo, Willisch Domínguez, Alfredo, Mosquera, José Antonio, Vela, Paloma, Tornero, Jesús, Sánchez-Fernández, Simón, Corominas, Héctor, Ramírez, Julio, López-Lasanta, María, Tortosa, Raül, Palau, Nuria, Alonso, Arnald, García-Montero, Andrés C, Gelpí, Josep Lluís, Codó, Laia, Day, Kenneth, Absher, Devin, Myers, Richard M, Cañete, Juan D, Marsal, Sara
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.10.2015; BMJ Publishing Group
• Subjects: ADAM Proteins - genetics; ADAMTS9 Protein; Adult; Aged; Arthritis; Arthritis, Psoriatic - genetics; Artritis; Autoimmune diseases; Biomedical research; Case-Control Studies; Cell Adhesion Molecules, Neuronal - genetics; Chromosomes; Collaboration; Consortia; Deoxyribonucleic acid; Dermatology; DNA; DNA Copy Number Variations; Female; Gene Deletion; Genetic Predisposition to Disease; Genetic testing; Genoma humà; Genome-Wide Association Study; Genomes; Genomics; Genotype; Genòmica; Human genome; Humans; Inflammatory bowel disease; Malalties autoimmunitàries; Male; Middle Aged; Patients; Psoriasi; Psoriasis; Psoriasis - genetics; Rheumatology; Risk Factors; Studies; Gene Polymorphism; Arthritis; Epidemiology; Psoriatic Arthritis
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2014-207190

ObjectiveCopy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach.MethodsA total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC).ResultsA total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3).ConclusionsThe present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk.