A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.
|Title||A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Julià, Antonio, Pinto José Antonio, Gratacós Jordi, Queiró Rubén, Ferrándiz Carlos, Fonseca Eduardo, Montilla Carlos, Torre-Alonso Juan Carlos, Puig Lluís, Venegas José Javier Pé, Nebro Antonio Fernández, Fernández Emilia, Muñoz-Fernández Santiago, Dauden Esteban, González Carlos, Roig Daniel, Carazo José Luís Sán, Zarco Pedro, Erra Alba, Estebaranz José Luís Lóp, Rodríguez Jesús, Ramírez David Moreno, de la Cueva Pablo, Vanaclocha Francisco, Herrera Enrique, Castañeda Santos, Rubio Esteban, Salvador Georgina, Díaz-Torné César, Blanco Ricardo, Domínguez Alfredo Willisch, 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 Andres C., Gelpí Josep-Lluis, Codó Laia, Day Kenneth, Absher Devin, Myers Richard M., Cañete Juan D., and Marsal Sara|
|Journal||Ann Rheum Dis|
|Date Published||2015 Oct|
|Keywords||ADAM Proteins, Adult, Aged, Arthritis, Case-Control Studies, Cell Adhesion Molecules, DNA Copy Number Variations, Female, Gene Deletion, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Neuronal, Psoriasis, Psoriatic, Risk Factors|
OBJECTIVE: Copy 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.
METHODS: A 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 χ(2) 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).
RESULTS: A 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).
CONCLUSIONS: The 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.