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A genome-wide association study identifies three new risk loci for Kawasaki disease

Abstract

We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10−21), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10−11) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10−8). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10−6) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.

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Figure 1: Genome-wide association results.

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Acknowledgements

We thank the individuals with Kawasaki disease and their families as well as all the medical staff taking care of them. We also thank members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan and members of the BioBank Japan project for supporting the study. We are grateful to T. Matsubara, M. Noshibatake, H. Aotsuka, H. Nakajima, F. Kudo, T. Sano, T. Matsushita, K. Suzuki, K. Akagi, T. Isobe, S. Ogita, S. Oku, T. Tanaka, Y. Tanaka, Y. Nomura, M. Sakauchi, H. Cho, A. Nariai, M. Miura, M. Nakagawa, Y. Kaburagi and other pediatricians who contributed Japanese DNA samples. We are also grateful to J. Pancheri and N. Innocentini for collecting US DNA samples. We thank D.A. Scherrer, S. Kawakami and Y. Nakashima for technical assistance. This work was supported by grants from the Millennium Project, from the Japan Kawasaki Disease Research Center and from the Ministry of Health, Labour and Welfare (0401040 to A.H.) and by a grant from the Heart, Lung, and Blood Institute of the US National Institutes of Health (HL-06941 to J.C.B.).

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Y.N. conceived the study. Y.N., N.K., T. Tanaka, A. Hata, M.K. and Y.O. designed the study. Y.O., K. Ozaki and M.K. performed the genotyping. J.C.B., C.S., M.T., H.S., K.Y., T. Saji, K. Ouchi, F.K., T.Y., T.N., K. Hamamoto, Y. Sato, H.H., T.H., T. Suenaga, T. Takeuchi, N.Y., A. Honda, H.K., J.S., S.S., M.M., K. Oishi, H.Y., N.A., S.I., R.M., Y.M., R.E., K. Higashi, Y.K. and S.T. provided samples and phenotype information. Y. Suzuki and K.S. managed clinical information. Y.O., A.T. and T. Tsunoda carried out statistical analysis. Y.O. designed and performed biological assays. Y.O., C.S., J.C.B. and T. Tanaka wrote the manuscript. All authors approved the final manuscript. The Japan Kawasaki Disease Genome Consortium and the US Kawasaki Disease Genetics Consortium contributed samples from Japanese and US individuals with Kawasaki disease, respectively.

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Correspondence to Yoshihiro Onouchi.

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Supplementary Note, Supplementary Figures 1–7 and Supplementary Tables 1–12 (PDF 3505 kb)

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Onouchi, Y., Ozaki, K., Burns, J. et al. A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet 44, 517–521 (2012). https://doi.org/10.1038/ng.2220

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