Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study
| Title: | Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study |
|---|---|
| Authors: | Borrego-Yaniz G.; Ortiz-Fernandez L.; Madrid-Paredes A.; Kerick M.; Hernandez-Rodriguez J.; Mackie S. L.; Vaglio A.; Castaneda S.; Solans R.; Mestre-Torres J.; Khalidi N.; Langford C. A.; Ytterberg S.; Beretta L.; Govoni M.; Emmi G.; Cimmino M. A.; Witte T.; Neumann T.; Holle J.; Schonau V.; Pugnet G.; Papo T.; Haroche J.; Mahr A.; Mouthon L.; Molberg O.; Diamantopoulos A. P.; Voskuyl A.; Daikeler T.; Berger C. T.; Molloy E. S.; Blockmans D.; van Sleen Y.; Iles M.; Sorensen L.; Luqmani R.; Reynolds G.; Bukhari M.; Bhagat S.; Ortego-Centeno N.; Brouwer E.; Lamprecht P.; Klapa S.; Salvarani C.; Merkel P. A.; Cid M. C.; Gonzalez-Gay M. A.; Morgan A. W.; Martin J.; Marquez A.; Callejas J. L.; Caminal-Montero L.; Corbera-Bellalta M.; de Miguel E.; Diaz-Lopez J. B.; Garcia-Villanueva M. J.; Gomez-Vaquero C.; Guijarro-Rojas M.; Hidalgo-Conde A.; Mari-Alfonso B.; Martinez-Berriochoa A.; Morado I. C.; Narvaez J.; Ramentol-Sintas M.; Martinez-Zapico A.; Martinez-Taboada V. M.; Miranda-Filloy J. A.; Monfort J.; Perez-Conesa M.; Prieto-Gonzalez S.; Raya E.; Rios-Fenandez R.; Sanchez-Martin J.; Sopena B.; Tio L.; Unzurrunzaga A.; Wordsworth O.; Whitwell I.; Brock J.; Douglas V.; Hettiarachchi C.; Bartholomew J.; Jarrett S.; Smithson G.; Green M.; Brown P. C.; Lawson C.; Gordon E.; Lane S.; Francis R.; Dasgupta B.; Masunda B.; Calver J.; Patel Y.; Thompson C.; Gregory L.; Levy S.; Menon A.; Thompson A.; Dyche L.; Martin M.; Li C.; Laxminarayan R.; Wilcox L.; de Guzman R.; Isaacs J.; Lorenzi A.; Farley R.; Hinchcliffe-Hume H.; Bejarano V.; Hope S.; Nandi P.; Stockham L.; Wilde C.; Durrant D.; Lloyd M.; Ye C. -S.; Stevens R.; Jilani A.; Collins D.; Pegler S.; Rivett A.; Price L.; McHugh N.; Skeoch S.; O'Kane D.; Kirkwood S.; Vadivelu S.; Pugmire S.; Sultan S.; Dooks E.; Armstrong L.; Sadik H.; Nandagudi A.; Abioye T.; Ramos A.; Gumus S.; Sofat N.; Harrison A.; Seward A.; Mollan S.; Rahan R.; Hawkins H.; Emsley H.; Bhargava A.; Fleming V.; Hare M.; Raj S.; George E.; Allen N.; Hunter K.; O'Sullivan E.; Bird G.; Magliano M.; Manzo K.; Sanghera B.; Hutchinson D.; Hammonds F.; Sharma P.; Cooper R.; McLintock G.; Al-Saffar Z. S.; Elliott K.; Neale T.; Mallinson J.; Lanyon P.; Pradere M. -J.; Jordan N.; Htut E. P.; Mushapaidzi T.; Abercrombie D.; Wright S.; Rowlands J.; Mukhtyar C.; Kennedy J.; Makkuni D.; Wilhelmsen E.; Kouroupis M.; John L.; Hughes R.; Walsh M.; Buckley M.; Mackay K.; Camden-Woodley T.; Redome J.; Pearce K.; Marianayagam T.; Cruz C.; Warner E.; Atchia I.; Walker C.; Black K.; Duffy S.; Fothergill L.; Jefferey R.; Toomey J.; Rhys-Dillon C.; Pothecary C.; Green L.; Toms T.; Maher L.; Davis D.; Sayan A.; Thankachen M.; Abusalameh M.; Record J.; Khan A.; Stafford S.; Hussein A.; Williams C.; Fletcher A.; Johson L.; Burnett R.; Moots R.; Frankland H.; Dale J.; Moar K.; Hollas C.; Parker B.; Ridings D.; Eapen S.; John S.; Robson J.; Guthrie L. B.; Fyfe R.; Tait M.; Marks J.; Gunter E.; Hernandez R.; Bhat S.; Johnston P.; Khurshid M.; Barclay C.; Kapur D.; Jeffrey H.; Hughes A.; Slack L.; Thomas E.; Royon A.; Hall A.; King J.; Nyathi S.; Morris V.; Castelino M.; Hawkins E.; Tomson L.; Singh A.; Nunag A.; O'Connor S.; Rushby N.; Hewitson N.; O'Sunmboye K.; Lewszuk A.; Boyles L.; Perry M.; Williams E.; Graver C.; Defever E.; Kamanth S.; Kay D.; Ogor J.; Winter L.; Horton S.; Welch G.; Hollinshead K.; Peters J.; Labao J.; Dmello A.; Dawson J.; Graham D.; De Lord D.; Deery J.; Hazelton T.; Carette S.; Chung S.; Cuthbertson D.; Forbess L. J.; Gewurz-Singer O.; Hoffman G. S.; Koening C. L.; Maksimowicz-McKinnon K. M.; McAlear C. A.; Moreland L. W.; Pagnoux C.; Seo P.; Specks U.; Spiera R. F.; Sreih A.; Warrington K. J.; Monach P. A.; Weisman M. |
| Contributors: | Borrego-Yaniz, G.; Ortiz-Fernandez, L.; Madrid-Paredes, A.; Kerick, M.; Hernandez-Rodriguez, J.; Mackie, S. L.; Vaglio, A.; Castaneda, S.; Solans, R.; Mestre-Torres, J.; Khalidi, N.; Langford, C. A.; Ytterberg, S.; Beretta, L.; Govoni, M.; Emmi, G.; Cimmino, M. A.; Witte, T.; Neumann, T.; Holle, J.; Schonau, V.; Pugnet, G.; Papo, T.; Haroche, J.; Mahr, A.; Mouthon, L.; Molberg, O.; Diamantopoulos, A. P.; Voskuyl, A.; Daikeler, T.; Berger, C. T.; Molloy, E. S.; Blockmans, D.; Van Sleen, Y.; Iles, M.; Sorensen, L.; Luqmani, R.; Reynolds, G.; Bukhari, M.; Bhagat, S.; Ortego-Centeno, N.; Brouwer, E.; Lamprecht, P.; Klapa, S.; Salvarani, C.; Merkel, P. A.; Cid, M. C.; Gonzalez-Gay, M. A.; Morgan, A. W.; Martin, J.; Marquez, A.; Callejas, J. L.; Caminal-Montero, L.; Corbera-Bellalta, M.; De Miguel, E.; Diaz-Lopez, J. B.; Garcia-Villanueva, M. J.; Gomez-Vaquero, C.; Guijarro-Rojas, M.; Hidalgo-Conde, A.; Mari-Alfonso, B.; Martinez-Berriochoa, A.; Morado, I. C.; Narvaez, J.; Ramentol-Sintas, M.; Martinez-Zapico, A.; Martinez-Taboada, V. M.; Miranda-Filloy, J. A.; Monfort, J.; Perez-Conesa, M.; Prieto-Gonzalez, S.; Raya, E.; Rios-Fenandez, R.; Sanchez-Martin, J.; Sopena, B.; Tio, L.; Unzurrunzaga, A.; Wordsworth, O.; Whitwell, I.; Brock, J.; Douglas, V.; Hettiarachchi, C.; Bartholomew, J.; Jarrett, S.; Smithson, G.; Green, M.; Brown, P. C.; Lawson, C.; Gordon, E.; Lane, S.; Francis, R.; Dasgupta, B.; Masunda, B.; Calver, J.; Patel, Y.; Thompson, C.; Gregory, L.; Levy, S.; Menon, A.; Thompson, A. |
| Publication Year: | 2024 |
| Collection: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| Description: | Background: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. Methods: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. Findings: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10–8; OR 1·19 [95% CI 1·12–1·26]) and VTN (rs704; p=2·75 × 10–9; OR 0·84 [0·79–0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10–8; OR 1·18 [1·12–1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs ... |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:001265814800001; volume:6; issue:6; firstpage:e374; lastpage:e383; journal:THE LANCET. RHEUMATOLOGY; https://hdl.handle.net/11380/1365960 |
| DOI: | 10.1016/S2665-9913(24)00064-X |
| Availability: | https://hdl.handle.net/11380/1365960; https://doi.org/10.1016/S2665-9913(24)00064-X |
| Rights: | info:eu-repo/semantics/openAccess ; license:[IR] creative-commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.F6BE082D |
| Database: | BASE |