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

Chiea Chuen Khor, Sonia Davila, Willemijn B. Breunis, Yi Ching Lee, Chisato Shimizu, Victoria J. Wright, Rae S M Yeung, Dennis E K Tan, Kar Seng Sim, Jie Jin Wang, Tien Yin Wong, Junxiong Pang, Paul Mitchell, Rolando Cimaz, Nagib Dahdah, Yiu Fai Cheung, Guo Ying Huang, Wanling Yang, In Sook Park, Jong Keuk LeeJer Yuarn Wu, Michael E Levin, Jane C. Burns, David Burgner, Taco W. Kuijpers, Martin L. Hibberd, 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, The Blue Mountains Eye Study

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Abstract

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. 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.

Original languageEnglish
Pages (from-to)1241-1246
Number of pages6
JournalNature Genetics
Volume43
Issue number12
DOIs
Publication statusPublished - 13 Nov 2011
Externally publishedYes

Cite this

Khor, C. C., Davila, S., Breunis, W. B., Lee, Y. C., Shimizu, C., Wright, V. J., ... The Blue Mountains Eye Study (2011). Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nature Genetics, 43(12), 1241-1246. https://doi.org/10.1038/ng.981
Khor, Chiea Chuen ; Davila, Sonia ; Breunis, Willemijn B. ; Lee, Yi Ching ; Shimizu, Chisato ; Wright, Victoria J. ; Yeung, Rae S M ; Tan, Dennis E K ; Sim, Kar Seng ; Wang, Jie Jin ; Wong, Tien Yin ; Pang, Junxiong ; Mitchell, Paul ; Cimaz, Rolando ; Dahdah, Nagib ; Cheung, Yiu Fai ; Huang, Guo Ying ; Yang, Wanling ; Park, In Sook ; Lee, Jong Keuk ; Wu, Jer Yuarn ; Levin, Michael E ; Burns, Jane C. ; Burgner, David ; Kuijpers, Taco W. ; Hibberd, Martin L. ; 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 ; The Blue Mountains Eye Study. / Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. In: Nature Genetics. 2011 ; Vol. 43, No. 12. pp. 1241-1246.
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abstract = "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. 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.",
author = "Khor, {Chiea Chuen} and Sonia Davila and Breunis, {Willemijn B.} and Lee, {Yi Ching} and Chisato Shimizu and Wright, {Victoria J.} and Yeung, {Rae S M} and Tan, {Dennis E K} and Sim, {Kar Seng} and Wang, {Jie Jin} and Wong, {Tien Yin} and Junxiong Pang and Paul Mitchell and Rolando Cimaz and Nagib Dahdah and Cheung, {Yiu Fai} and Huang, {Guo Ying} and Wanling Yang and Park, {In Sook} and Lee, {Jong Keuk} and Wu, {Jer Yuarn} and Levin, {Michael E} and Burns, {Jane C.} and David Burgner and Kuijpers, {Taco W.} and Hibberd, {Martin L.} and {Hong Kong–Shanghai Kawasaki Disease Genetics Consortium} and Ma, {Xiao Jing} and {Korean Kawasaki Disease Genetics Consortium} and {Taiwan Kawasaki Disease Genetics Consortium} and {International Kawasaki Disease Genetics Consortium} and {US Kawasaki Disease Genetics Consortium} and {The Blue Mountains Eye Study}",
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Khor, CC, Davila, S, Breunis, WB, Lee, YC, Shimizu, C, Wright, VJ, Yeung, RSM, Tan, DEK, Sim, KS, Wang, JJ, Wong, TY, Pang, J, Mitchell, P, Cimaz, R, Dahdah, N, Cheung, YF, Huang, GY, Yang, W, Park, IS, Lee, JK, Wu, JY, Levin, ME, 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 & The Blue Mountains Eye Study 2011, 'Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease', Nature Genetics, vol. 43, no. 12, pp. 1241-1246. https://doi.org/10.1038/ng.981

Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. / Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B.; Lee, Yi Ching; Shimizu, Chisato; Wright, Victoria J.; Yeung, Rae S M; Tan, Dennis E K; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu Fai; Huang, Guo Ying; Yang, Wanling; Park, In Sook; Lee, Jong Keuk; Wu, Jer Yuarn; Levin, Michael E; Burns, Jane C.; Burgner, David; Kuijpers, Taco W.; Hibberd, Martin L.; 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; The Blue Mountains Eye Study.

In: Nature Genetics, Vol. 43, No. 12, 13.11.2011, p. 1241-1246.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease

AU - Khor, Chiea Chuen

AU - Davila, Sonia

AU - Breunis, Willemijn B.

AU - Lee, Yi Ching

AU - Shimizu, Chisato

AU - Wright, Victoria J.

AU - Yeung, Rae S M

AU - Tan, Dennis E K

AU - Sim, Kar Seng

AU - Wang, Jie Jin

AU - Wong, Tien Yin

AU - Pang, Junxiong

AU - Mitchell, Paul

AU - Cimaz, Rolando

AU - Dahdah, Nagib

AU - Cheung, Yiu Fai

AU - Huang, Guo Ying

AU - Yang, Wanling

AU - Park, In Sook

AU - Lee, Jong Keuk

AU - Wu, Jer Yuarn

AU - Levin, Michael E

AU - Burns, Jane C.

AU - Burgner, David

AU - Kuijpers, Taco W.

AU - Hibberd, Martin L.

AU - Hong Kong–Shanghai Kawasaki Disease Genetics Consortium

AU - Ma, Xiao Jing

AU - Korean Kawasaki Disease Genetics Consortium

AU - Taiwan Kawasaki Disease Genetics Consortium

AU - International Kawasaki Disease Genetics Consortium

AU - US Kawasaki Disease Genetics Consortium

AU - The Blue Mountains Eye Study

PY - 2011/11/13

Y1 - 2011/11/13

N2 - 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. 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.

AB - 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. 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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U2 - 10.1038/ng.981

DO - 10.1038/ng.981

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Khor CC, Davila S, Breunis WB, Lee YC, Shimizu C, Wright VJ et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nature Genetics. 2011 Nov 13;43(12):1241-1246. https://doi.org/10.1038/ng.981