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Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis

Abstract

To find new candidate loci predisposing individuals to Kawasaki disease, an acute vasculitis that affects children, we conducted a genome-wide association study in 622 individuals with Kawasaki disease (cases) and 1,107 controls in a Han Chinese population residing in Taiwan, with replication in an independent Han Chinese sample of 261 cases and 550 controls. We report two new loci, one at BLK (encoding B-lymphoid tyrosine kinase) and one at CD40, that are associated with Kawasaki disease at genome-wide significance (P < 5 × 10−8). Our findings may lead to a better understanding of the role of immune activation and inflammation in Kawasaki disease pathogenesis.

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Figure 1: Results of genome-wide association analysis (−log10 P) shown in chromosomal order for 716,935 SNPs tested for association in initial sample of 622 Kawasaki disease cases and 1,107 controls.
Figure 2: Association plots for the BLK and CD40 regions.

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Acknowledgements

We thank all affected individuals and their families who devoted their time and effort to participate in this study. We gratefully acknowledge the members of the Translational Resource Center (TRC) (NSC100-2325-B-001-023) for Genomic Medicine and the National Center for Genome Medicine (NCGM) (NSC100-2319-B-001-001) at Academia Sinica for their support in subject recruitment, genotyping and statistical analysis. We especially thank H. Lue for his inspirational discussion. This study was supported by the Academia Sinica Genomic Medicine Multicenter Study, Taiwan (40-05-GMM). The funders had no role in study design, data collection or analysis, the decision to publish or preparation of the manuscript.

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Contributions

Y.-T.C., F.-J.T. and J.-Y.W. are the principal investigators who conceived and obtained funding for this project. Y.-C.L., C.-H.C. and J.-Y.W. organized and supervised the GWAS and replication genotyping pipeline and devised the overall analysis plan. Y.-C.L. wrote the first draft of the manuscript with input from C.-H.C. and J.-Y.W. Y.-C.L., L.-C.C. and C.-H.C. analyzed the data. C.-D.L., J.-S.C., L.-Y.C., L.-M.H., M.-R.C., H.-C.K., H.C., F.-Y.H., M.-L.L., Y.-C.H., B.H., N.-C.C., K.-P.H., P.-C.L., Y.-M.L., Y.-J.C. and the Taiwan Pediatric ID Alliance coordinated and contributed subject and database phenotype collections.

Corresponding authors

Correspondence to Yuan-Tsong Chen, Fuu-Jen Tsai or Jer-Yuarn Wu.

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The authors declare no competing financial interests.

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Supplementary Note, Supplementary Figures 1–5 and Supplementary Tables 1–9 (PDF 1847 kb)

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Lee, YC., Kuo, HC., Chang, JS. et al. Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis. Nat Genet 44, 522–525 (2012). https://doi.org/10.1038/ng.2227

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