Author/Editor		Carmona, Elio G; García-Giménez, Jose A.; López-Mejías, Raquel; Chuen Khor, Chiea; Lee, Jong-Keuk; Taskiran, Ekim; Ozen, Seza; Hočevar, Alojzija; Gorenjak, Mario; Potočnik, Uroš
Title		Identification of a shared genetic risk locus for Kawasaki disease and IgA vasculitis by a cross-phenotype meta-analysis
Type		članek
Publication year		2022
Volume		str. str.
ISSN		1462-0324 - Rheumatology (Oxford, England)
Language		eng
Abstract		Objectives: Combination 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 (kDa) and IgA vasculitis (IgAV) by performing the first comprehensive large-scale analysis on the genetic overlap between both pediatric vasculitis. Methods: A total of 1,190 vasculitis patients and 11 302 healthy controls were analyzed. First, in the discovery phase, genome-wide data of 405 kDa patients and 6,252 controls and 215 IgAV patients and 1,324 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 3,726 controls). Polymorphisms with p-values r 5x1 0 -8 in the global IgAV-kDa 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= 8.06x10-10). Additionally, when IgAV was individually analyzed, a strong association between rs3743841 and this vasculitis was also evident (p= 1.25x10-7; OR (95% CI)=1.47 (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 have identified a new risk locus with pleiotropic effects on the two vasculitis of childhood analyzed. This locus represents the strongest non-HLA signal described for IgAV to date.
Keywords		IgA vaskulitis Kawasakijeva bolezen študija asociacije na celotnem genomu IgA vasculitis Kawasaki disease genome-wide association study