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• W2902395823 startingPage "13045" @default.
• W2902395823 abstract "Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted. We identified four unreported significant loci, namely rs2322599, rs103294, rs17133698, and rs1713450, in PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, respectively. Two additional significant loci unreported in non-European GWAS were identified, namely HSPA6/FCGR3A and chr21q.22. We found that a single variant associated with the expression of MICB, a ligand for natural killer (NK) cell receptor, could explain the entire association with the HLA-B region. Rs2322599 is strongly associated with the expression of PTK2B Rs103294 risk allele in LILRA3/LILRB2 is known to be a tagging SNP for the deletion of LILRA3, a soluble receptor of HLA class I molecules. We found a significant epistasis effect between HLA-B*52 and rs103294 (P = 1.2 × 10-3). Enhancer enrichment analysis and pathway analysis suggested the involvement of NK cells (P = 8.8 × 10-5, enhancer enrichment). In conclusion, four unreported TAK susceptibility loci and an epistasis effect between LILRA3 and HLA-B*52 were identified. HLA and non-HLA regions suggested a critical role for NK cells in TAK." @default.
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• W2902395823 date "2018-11-29" @default.
• W2902395823 modified "2023-10-02" @default.
• W2902395823 title "Genetic determinants and an epistasis of <i>LILRA3</i> and HLA-B*52 in Takayasu arteritis" @default.
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• W2902395823 doi "https://doi.org/10.1073/pnas.1808850115" @default.
• W2902395823 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6304955" @default.
• W2902395823 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30498034" @default.
• W2902395823 hasPublicationYear "2018" @default.
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