title: A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.
abstract: 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.
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Julià
authors.affiliation: Rheumatology Department, Complejo Hospitalario Juan Canalejo, A Coruña, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Pinto
authors.affiliation: Rheumatology Department, Hospital Parc Taulí, Sabadell, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Gratacós
authors.affiliation: Rheumatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Queiró
authors.affiliation: Dermatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferrándiz
authors.affiliation: Dermatology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fonseca
authors.affiliation: Rheumatology Department, Hospital Virgen de la Vega, Salamanca, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Montilla
authors.affiliation: Rheumatology Department, Hospital Monte Naranco, Oviedo, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Torre-Alonso
authors.affiliation: Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Puig
authors.affiliation: Rheumatology Department, Hospital de Jerez de la Frontera, Cádiz, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Pérez Venegas
authors.affiliation: UGC Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández Nebro
authors.affiliation: Department of Dermatology, Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Emilia
authors.initials: E
authors.lastname: Fernández
authors.affiliation: Rheumatology Department, Hospital Universitario Infanta Sofía, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Muñoz-Fernández
authors.affiliation: Dermatology Department, Hospital Universitario La Princesa, Madrid, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Daudén
authors.affiliation: Rheumatology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: González
authors.affiliation: Rheumatology Service, Hospital Moisès Broggi, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roig
authors.affiliation: Dermatology Department, Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: José Luís
authors.initials: JL
authors.lastname: Sánchez Carazo
authors.affiliation: Rheumatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Zarco
authors.affiliation: Rheumatology Department, Hospital Sant Rafael, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Erra
authors.affiliation: Dermatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: José Luís
authors.initials: JL
authors.lastname: López Estebaranz
authors.affiliation: Rheumatology Department, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez
authors.affiliation: Dermatology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: David Moreno
authors.initials: DM
authors.lastname: Ramírez
authors.affiliation: Department of Dermatology, Hospital Universitario Infanta Leonor, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: de la Cueva
authors.affiliation: Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vanaclocha
authors.affiliation: Dermatology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrera
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Rheumatology Department, Centro de Salud Virgen de los Reyes, Sevilla, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Rubio
authors.affiliation: Rheumatology Department, Hospital Mútua de Terrassa, Terrassa, Spain.
authors.forename: Georgina
authors.initials: G
authors.lastname: Salvador
authors.affiliation: Rheumatology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Díaz-Torné
authors.affiliation: Rheumatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Rheumatology Department, Complexo Hospitalario de Ourense, Ourense, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Willisch Domínguez
authors.affiliation: Rheumatology Department, Complejo Hospitalario Hospital Provincial de Pontevedra, Pontevedra, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Mosquera
authors.affiliation: Rheumatology Department, Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Vela
authors.affiliation: Rheumatology Department, Hospital Universitario Guadalajara, Guadalajara, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Tornero
authors.affiliation: Rheumatology Department, Hospital La Mancha Centro, Alcázar de San Juan, Spain.
authors.forename: Simón
authors.initials: S
authors.lastname: Sánchez-Fernández
authors.affiliation: Rheumatology Service, Hospital Moisès Broggi, Barcelona, Spain.
authors.forename: Héctor
authors.initials: H
authors.lastname: Corominas
authors.affiliation: Rheumatology Department, Hospital Clínic de Barcelona and IDIBAPS, Barcelona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Ramírez
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: López-Lasanta
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Raül
authors.initials: R
authors.lastname: Tortosa
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Palau
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Arnald
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Banco Nacional de ADN Carlos III, University of Salamanca, Salamanca, Spain.
authors.forename: Andrés C
authors.initials: AC
authors.lastname: García-Montero
authors.affiliation: Life Sciences, Barcelona Supercomputing Centre, National Institute of Bioinformatics, Barcelona, Spain.
authors.forename: Josep Lluís
authors.initials: JL
authors.lastname: Gelpí
authors.affiliation: HudsonAlpha Institute for Biotechnology, Alabama, USA.
authors.forename: Laia
authors.initials: L
authors.lastname: Codó
authors.affiliation: HudsonAlpha Institute for Biotechnology, Alabama, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Day
authors.affiliation: HudsonAlpha Institute for Biotechnology, Alabama, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.affiliation: HudsonAlpha Institute for Biotechnology, Alabama, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.affiliation: Rheumatology Department, Hospital Clínic de Barcelona and IDIBAPS, Barcelona, Spain.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Cañete
authors.affiliation: Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Marsal
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071119:ADAMTS9 Protein; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000235:genetics*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D051528:Guanylate Kinases; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D051528:Guanylate Kinases; C113338:MAGI1 protein, human; D051722:ADAM Proteins; D000071119:ADAMTS9 Protein; C412869:ADAMTS9 protein, human
keywords: Arthritis; Epidemiology; Gene Polymorphism; Psoriatic Arthritis