Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis

Carmona E. G., Garcia-Gimenez J. A., Lopez-Mejias R., Khor C. C., Lee J., Taskiran E., ...More

RHEUMATOLOGY, vol.61, no.3, pp.1204-1210, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 61 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1093/rheumatology/keab443
  • Journal Name: RHEUMATOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CINAHL, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Page Numbers: pp.1204-1210
  • Keywords: IgA vasculitis, Kawasaki disease, genome-wide association study, single-nucleotide polymorphism, HENOCH-SCHONLEIN PURPURA, ASSOCIATION
  • Hacettepe University Affiliated: Yes


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 x 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 x 10(-10)). Additionally, when IgAV was individually analysed, a strong association between rs3743841 and this vasculitis was also evident [P = 1.25 x 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.