Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing.
Autoimmunity
Polymorphism, Genetic
Systemic vasculitis
Journal
Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
30
11
2022
accepted:
04
02
2023
medline:
15
5
2023
pubmed:
17
2
2023
entrez:
16
2
2023
Statut:
ppublish
Résumé
The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap. Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis. Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis.
Identifiants
pubmed: 36797040
pii: ard-2022-223697
doi: 10.1136/ard-2022-223697
pmc: PMC10314028
doi:
Substances chimiques
CTLA-4 Antigen
0
TRIM35 protein, human
0
Apoptosis Regulatory Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
837-847Subventions
Organisme : British Heart Foundation
ID : PG/13/64/30435
Pays : United Kingdom
Organisme : NIAMS NIH HHS
ID : R01 AR070148
Pays : United States
Organisme : NIAMS NIH HHS
ID : U54 AR057319
Pays : United States
Organisme : NCRR NIH HHS
ID : U54 RR019497
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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