Antonio Julià1, José Antonio Pinto2, Jordi Gratacós3, Rubén Queiró4, Carlos Ferrándiz5, Eduardo Fonseca6, Carlos Montilla7, Juan Carlos Torre-Alonso8, Lluís Puig9, José Javier Pérez Venegas10, Antonio Fernández Nebro11, Emilia Fernández12, Santiago Muñoz-Fernández13, Esteban Daudén14, Carlos González15, Daniel Roig16, José Luís Sánchez Carazo17, Pedro Zarco18, Alba Erra19, José Luís López Estebaranz20, Jesús Rodríguez21, David Moreno Ramírez22, Pablo de la Cueva23, Francisco Vanaclocha24, Enrique Herrera25, Santos Castañeda26, Esteban Rubio27, Georgina Salvador28, César Díaz-Torné29, Ricardo Blanco30, Alfredo Willisch Domínguez31, José Antonio Mosquera32, Paloma Vela33, Jesús Tornero34, Simón Sánchez-Fernández35, Héctor Corominas16, Julio Ramírez36, María López-Lasanta1, Raül Tortosa1, Nuria Palau1, Arnald Alonso1, Andrés C García-Montero37, Josep Lluís Gelpí38, Laia Codó39, Kenneth Day39, Devin Absher39, Richard M Myers39, Juan D Cañete36, Sara Marsal1. 1. Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain. 2. Rheumatology Department, Complejo Hospitalario Juan Canalejo, A Coruña, Spain. 3. Rheumatology Department, Hospital Parc Taulí, Sabadell, Barcelona, Spain. 4. Rheumatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain. 5. Dermatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. 6. Dermatology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain. 7. Rheumatology Department, Hospital Virgen de la Vega, Salamanca, Spain. 8. Rheumatology Department, Hospital Monte Naranco, Oviedo, Spain. 9. Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 10. Rheumatology Department, Hospital de Jerez de la Frontera, Cádiz, Spain. 11. UGC Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain. 12. Department of Dermatology, Hospital Universitario de Salamanca, Salamanca, Spain. 13. Rheumatology Department, Hospital Universitario Infanta Sofía, Madrid, Spain. 14. Dermatology Department, Hospital Universitario La Princesa, Madrid, Spain. 15. Rheumatology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain. 16. Rheumatology Service, Hospital Moisès Broggi, Barcelona, Spain. 17. Dermatology Department, Hospital General Universitario de Valencia, Valencia, Spain. 18. Rheumatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 19. Rheumatology Department, Hospital Sant Rafael, Barcelona, Spain. 20. Dermatology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 21. Rheumatology Department, Hospital Universitari de Bellvitge, Barcelona, Spain. 22. Dermatology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain. 23. Department of Dermatology, Hospital Universitario Infanta Leonor, Madrid, Spain. 24. Dermatology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. 25. Dermatology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain. 26. Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain. 27. Rheumatology Department, Centro de Salud Virgen de los Reyes, Sevilla, Spain. 28. Rheumatology Department, Hospital Mútua de Terrassa, Terrassa, Spain. 29. Rheumatology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 30. Rheumatology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 31. Rheumatology Department, Complexo Hospitalario de Ourense, Ourense, Spain. 32. Rheumatology Department, Complejo Hospitalario Hospital Provincial de Pontevedra, Pontevedra, Spain. 33. Rheumatology Department, Hospital General Universitario de Alicante, Alicante, Spain. 34. Rheumatology Department, Hospital Universitario Guadalajara, Guadalajara, Spain. 35. Rheumatology Department, Hospital La Mancha Centro, Alcázar de San Juan, Spain. 36. Rheumatology Department, Hospital Clínic de Barcelona and IDIBAPS, Barcelona, Spain. 37. Banco Nacional de ADN Carlos III, University of Salamanca, Salamanca, Spain. 38. Life Sciences, Barcelona Supercomputing Centre, National Institute of Bioinformatics, Barcelona, Spain. 39. HudsonAlpha Institute for Biotechnology, Alabama, USA.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Jun-Ichi Abe; Kyung Ae Ko; Sivareddy Kotla; Yin Wang; Jesus Paez-Mayorga; Ik Jae Shin; Masaki Imanishi; Hang Thi Vu; Yunting Tao; Miguel M Leiva-Juarez; Tamlyn N Thomas; Jan L Medina; Jong Hak Won; Yuka Fujii; Carolyn J Giancursio; Elena McBeath; Ji-Hyun Shin; Liliana Guzman; Rei J Abe; Jack Taunton; Naoki Mochizuki; William Faubion; John P Cooke; Keigi Fujiwara; Scott E Evans; Nhat-Tu Le Journal: JCI Insight Date: 2019-04-04
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Authors: Jessica A Hensel; Sarah-Anne E Nicholas; Amy L Kimble; Arjun S Nagpal; Omar M F Omar; Jordan D Tyburski; Evan R Jellison; Antoine Ménoret; Manabu Ozawa; Annabelle Rodriguez-Oquendo; Anthony T Vella; Patrick A Murphy Journal: Proc Natl Acad Sci U S A Date: 2022-07-18 Impact factor: 12.779
Authors: Michelle L M Mulder; Tamara W van Hal; Mark H Wenink; Hans J P M Koenen; Frank H J van den Hoogen; Elke M G J de Jong; Juul M P A van den Reek; Johanna E Vriezekolk Journal: Arthritis Res Ther Date: 2021-06-14 Impact factor: 5.156
Authors: Pedro P Perrotti; Adrià Aterido; Antonio Fernández-Nebro; Juan D Cañete; Carlos Ferrándiz; Jesús Tornero; Javier P Gisbert; Eugeni Domènech; Benjamín Fernández-Gutiérrez; Fernando Gomollón; Esther García-Planella; Emilia Fernández; Raimon Sanmartí; Jordi Gratacós; Víctor Manuel Martínez-Taboada; Luís Rodríguez-Rodríguez; Núria Palau; Raül Tortosa; Mireia L Corbeto; María L Lasanta; Sara Marsal; Antonio Julià Journal: PLoS One Date: 2017-10-05 Impact factor: 3.240