Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis.
Rheumatology (Oxford)
; 61(3): 1204-1210, 2022 03 02.
Article
em En
| MEDLINE
| ID: mdl-33993232
ABSTRACT
OBJECTIVES:
Combining of genomic data of different pathologies as a single phenotype has emerged as a useful strategy to identify genetic risk loci shared among immune-mediated diseases. Our study aimed to increase our knowledge of the genetic contribution to Kawasaki disease (KD) and IgA vasculitis (IgAV) by performing the first comprehensive large-scale analysis on the genetic overlap between them.METHODS:
A total of 1190 vasculitis patients and 11 302 healthy controls were analysed. First, in the discovery phase, genome-wide data of 405 KD patients and 6252 controls and 215 IgAV patients and 1324 controls, all of European origin, were combined using an inverse variance meta-analysis. Second, the top associated polymorphisms were selected for replication in additional independent cohorts (570 cases and 3726 controls). Polymorphisms with P-values ≤5 × 10-8 in the global IgAV-KD meta-analysis were considered as shared genetic risk loci.RESULTS:
A genetic variant, rs3743841, located in an intron of the NAGPA gene, reached genome-wide significance in the cross-disease meta-analysis (P = 8.06 × 10-10). Additionally, when IgAV was individually analysed, a strong association between rs3743841 and this vasculitis was also evident [P = 1.25 × 10-7; odds ratio = 1.47 (95% CI 1.27, 1.69)]. In silico functional annotation showed that this polymorphism acts as a regulatory variant modulating the expression levels of the NAGPA and SEC14L5 genes.CONCLUSION:
We identified a new risk locus with pleiotropic effects on the two childhood vasculitides analysed. This locus represents the strongest non-HLA signal described for IgAV to date.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasculite por IgA
/
Diester Fosfórico Hidrolases
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Síndrome de Linfonodos Mucocutâneos
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Rheumatology (Oxford)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article