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Extended report
A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk
  1. Antonio Julià1,
  2. José Antonio Pinto2,
  3. Jordi Gratacós3,
  4. Rubén Queiró4,
  5. Carlos Ferrándiz5,
  6. Eduardo Fonseca6,
  7. Carlos Montilla7,
  8. Juan Carlos Torre-Alonso8,
  9. Lluís Puig9,
  10. José Javier Pérez Venegas10,
  11. Antonio Fernández Nebro11,
  12. Emilia Fernández12,
  13. Santiago Muñoz-Fernández13,
  14. Esteban Daudén14,
  15. Carlos González15,
  16. Daniel Roig16,
  17. José Luís Sánchez Carazo17,
  18. Pedro Zarco18,
  19. Alba Erra19,
  20. José Luís López Estebaranz20,
  21. Jesús Rodríguez21,
  22. David Moreno Ramírez22,
  23. Pablo de la Cueva23,
  24. Francisco Vanaclocha24,
  25. Enrique Herrera25,
  26. Santos Castañeda26,
  27. Esteban Rubio27,
  28. Georgina Salvador28,
  29. César Díaz-Torné29,
  30. Ricardo Blanco30,
  31. Alfredo Willisch Domínguez31,
  32. José Antonio Mosquera32,
  33. Paloma Vela33,
  34. Jesús Tornero34,
  35. Simón Sánchez-Fernández35,
  36. Héctor Corominas16,
  37. Julio Ramírez36,
  38. María López-Lasanta1,
  39. Raül Tortosa1,
  40. Nuria Palau1,
  41. Arnald Alonso1,
  42. Andrés C García-Montero37,
  43. Josep Lluís Gelpí38,
  44. Laia Codó39,
  45. Kenneth Day39,
  46. Devin Absher39,
  47. Richard M Myers39,
  48. Juan D Cañete36,
  49. Sara Marsal1
  1. 1Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain
  2. 2Rheumatology Department, Complejo Hospitalario Juan Canalejo, A Coruña, Spain
  3. 3Rheumatology Department, Hospital Parc Taulí, Sabadell, Barcelona, Spain
  4. 4Rheumatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
  5. 5Dermatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
  6. 6Dermatology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain
  7. 7Rheumatology Department, Hospital Virgen de la Vega, Salamanca, Spain
  8. 8Rheumatology Department, Hospital Monte Naranco, Oviedo, Spain
  9. 9Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  10. 10Rheumatology Department, Hospital de Jerez de la Frontera, Cádiz, Spain
  11. 11UGC Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
  12. 12Department of Dermatology, Hospital Universitario de Salamanca, Salamanca, Spain
  13. 13Rheumatology Department, Hospital Universitario Infanta Sofía, Madrid, Spain
  14. 14Dermatology Department, Hospital Universitario La Princesa, Madrid, Spain
  15. 15Rheumatology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain
  16. 16Rheumatology Service, Hospital Moisès Broggi, Barcelona, Spain
  17. 17Dermatology Department, Hospital General Universitario de Valencia, Valencia, Spain
  18. 18Rheumatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain
  19. 19Rheumatology Department, Hospital Sant Rafael, Barcelona, Spain
  20. 20Dermatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain
  21. 21Rheumatology Department, Hospital Universitari de Bellvitge, Barcelona, Spain
  22. 22Dermatology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain
  23. 23Department of Dermatology, Hospital Universitario Infanta Leonor, Madrid, Spain
  24. 24Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
  25. 25Dermatology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain
  26. 26Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain
  27. 27Rheumatology Department, Centro de Salud Virgen de los Reyes, Sevilla, Spain
  28. 28Rheumatology Department, Hospital Mútua de Terrassa, Terrassa, Spain
  29. 29Rheumatology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  30. 30Rheumatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain
  31. 31Rheumatology Department, Complexo Hospitalario de Ourense, Ourense, Spain
  32. 32Rheumatology Department, Complejo Hospitalario Hospital Provincial de Pontevedra, Pontevedra, Spain
  33. 33Rheumatology Department, Hospital General Universitario de Alicante, Alicante, Spain
  34. 34Rheumatology Department, Hospital Universitario Guadalajara, Guadalajara, Spain
  35. 35Rheumatology Department, Hospital La Mancha Centro, Alcázar de San Juan, Spain
  36. 36Rheumatology Department, Hospital Clínic de Barcelona and IDIBAPS, Barcelona, Spain
  37. 37Banco Nacional de ADN Carlos III, University of Salamanca, Salamanca, Spain
  38. 38Life Sciences, Barcelona Supercomputing Centre, National Institute of Bioinformatics, Barcelona, Spain
  39. 39HudsonAlpha Institute for Biotechnology, Alabama, USA
  1. Correspondence to Professor Sara Marsal, Rheumatology Research Group, Vall d'Hebron University Hospital, Pg Vall d'Hebron, 119-129, Barcelona 08035, Spain; sara.marsal{at}vhir.org

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 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).

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.

  • Psoriatic Arthritis
  • Gene Polymorphism
  • Epidemiology
  • Arthritis

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