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Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.

Publication ,  Journal Article
Khor, CC; Davila, S; Breunis, WB; Lee, Y-C; Shimizu, C; Wright, VJ; Yeung, RSM; Tan, DEK; Sim, KS; Wang, JJ; Wong, TY; Pang, J; Mitchell, P ...
Published in: Nat Genet
November 13, 2011

Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

November 13, 2011

Volume

43

Issue

12

Start / End Page

1241 / 1246

Location

United States

Related Subject Headings

  • Receptors, IgG
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Multigene Family
  • Mucocutaneous Lymph Node Syndrome
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

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Khor, C. C., Davila, S., Breunis, W. B., Lee, Y.-C., Shimizu, C., Wright, V. J., … Blue Mountains Eye Study, . (2011). Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet, 43(12), 1241–1246. https://doi.org/10.1038/ng.981
Khor, Chiea Chuen, Sonia Davila, Willemijn B. Breunis, Yi-Ching Lee, Chisato Shimizu, Victoria J. Wright, Rae S. M. Yeung, et al. “Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.Nat Genet 43, no. 12 (November 13, 2011): 1241–46. https://doi.org/10.1038/ng.981.
Khor CC, Davila S, Breunis WB, Lee Y-C, Shimizu C, Wright VJ, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet. 2011 Nov 13;43(12):1241–6.
Khor, Chiea Chuen, et al. “Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.Nat Genet, vol. 43, no. 12, Nov. 2011, pp. 1241–46. Pubmed, doi:10.1038/ng.981.
Khor CC, Davila S, Breunis WB, Lee Y-C, Shimizu C, Wright VJ, Yeung RSM, Tan DEK, Sim KS, Wang JJ, Wong TY, Pang J, Mitchell P, Cimaz R, Dahdah N, Cheung Y-F, Huang G-Y, Yang W, Park I-S, Lee J-K, Wu J-Y, Levin M, Burns JC, Burgner D, Kuijpers TW, Hibberd ML, Hong Kong–Shanghai Kawasaki Disease Genetics Consortium, Korean Kawasaki Disease Genetics Consortium, Taiwan Kawasaki Disease Genetics Consortium, International Kawasaki Disease Genetics Consortium, US Kawasaki Disease Genetics Consortium, Blue Mountains Eye Study. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet. 2011 Nov 13;43(12):1241–1246.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

November 13, 2011

Volume

43

Issue

12

Start / End Page

1241 / 1246

Location

United States

Related Subject Headings

  • Receptors, IgG
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Multigene Family
  • Mucocutaneous Lymph Node Syndrome
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease