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 Lee & 85 others Jer Yuarn Wu, Michael Levin, Jane C. Burns, David Burgner, Taco W. Kuijpers, Martin L. Hibberd, Yu Lung Lau, Jing Zhang, Xiao Jing Ma, Fang Liu, Lin Wu, Jeong Jin Yoo, Soo Jong Hong, Kwi Joo Kim, Jae Jung Kim, Young Mi Park, Young Mi Hong, Sejung Sohn, Giyoung Jang, Kee Soo Ha, Hyo-Kyoung Nam, Jung Hye Byeon, Sin Weon Yun, Myung Ki Han, Kyung Yil Lee, Ja Young Hwang, Jung Woo Rhim, Min Seob Song, Hyoung Doo Lee, Dong Soo Kim, Jae Moo Lee, Jeng Sheng Chang, Fuu Jen Tsai, Chi Di Liang, Ming Ren Chen, Hsin Chi, Nan Chang Chiu, Fu Yuan Huang, Luan Yin Chang, Li Min Huang, Ho Chang Kuo, Kao Pin Huang, Meng Luen Lee, Betau Hwang, Yhu Chering Huang, Pi Chang Lee, Miranda Odam, Frank T. Christiansen, Campbell Witt, Paul Goldwater, Nigel Curtis, Pamela Palasanthiran, John Ziegler, Michael Nissen, Clare Nourse, Irene M. Kuipers, Jaap J. Ottenkamp, Judy Geissler, Maarten Biezeveld, Carline Tacke, Luc Filippini, Paul Brogan, Nigel Klein, Vanita Shah, Michael Dillon, Robert Booy, Delane Shingadia, Anu Bose, Thomas Mukasa, Robert Tulloh, Colin Michie, Jane W. Newburger, Annette L. Baker, Anne H. Rowley, Stanford T. Shulman, Wilbert Mason, Masato Takahashi, Marian E. Melish, Adriana H. Tremoulet, Ananth Viswanathan, Elena Rochtchina, John Attia, Rodney Scott, Elizabeth Holliday, Stephen Harrap

Research output: Contribution to journalArticle

178 Citations (Scopus)

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 - 2011 Dec 1

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Mucocutaneous Lymph Node Syndrome
Genome-Wide Association Study
Odds Ratio
IgG Receptors
Systemic Vasculitis
Intravenous Immunoglobulins
Disease Susceptibility
Single Nucleotide Polymorphism
Alleles
Genome
Genes
Therapeutics

ASJC Scopus subject areas

  • Genetics

Cite this

Khor, C. C., Davila, S., Breunis, W. B., Lee, Y. C., Shimizu, C., Wright, V. J., ... Harrap, S. (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

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; Burns, Jane C.; Burgner, David; Kuijpers, Taco W.; Hibberd, Martin L.; Lau, Yu Lung; Zhang, Jing; Ma, Xiao Jing; Liu, Fang; Wu, Lin; Yoo, Jeong Jin; Hong, Soo Jong; Kim, Kwi Joo; Kim, Jae Jung; Park, Young Mi; Hong, Young Mi; Sohn, Sejung; Jang, Giyoung; Ha, Kee Soo; Nam, Hyo-Kyoung; Byeon, Jung Hye; Yun, Sin Weon; Han, Myung Ki; Lee, Kyung Yil; Hwang, Ja Young; Rhim, Jung Woo; Song, Min Seob; Lee, Hyoung Doo; Kim, Dong Soo; Lee, Jae Moo; Chang, Jeng Sheng; Tsai, Fuu Jen; Liang, Chi Di; Chen, Ming Ren; Chi, Hsin; Chiu, Nan Chang; Huang, Fu Yuan; Chang, Luan Yin; Huang, Li Min; Kuo, Ho Chang; Huang, Kao Pin; Lee, Meng Luen; Hwang, Betau; Huang, Yhu Chering; Lee, Pi Chang; Odam, Miranda; Christiansen, Frank T.; Witt, Campbell; Goldwater, Paul; Curtis, Nigel; Palasanthiran, Pamela; Ziegler, John; Nissen, Michael; Nourse, Clare; Kuipers, Irene M.; Ottenkamp, Jaap J.; Geissler, Judy; Biezeveld, Maarten; Tacke, Carline; Filippini, Luc; Brogan, Paul; Klein, Nigel; Shah, Vanita; Dillon, Michael; Booy, Robert; Shingadia, Delane; Bose, Anu; Mukasa, Thomas; Tulloh, Robert; Michie, Colin; Newburger, Jane W.; Baker, Annette L.; Rowley, Anne H.; Shulman, Stanford T.; Mason, Wilbert; Takahashi, Masato; Melish, Marian E.; Tremoulet, Adriana H.; Viswanathan, Ananth; Rochtchina, Elena; Attia, John; Scott, Rodney; Holliday, Elizabeth; Harrap, Stephen.

In: Nature Genetics, Vol. 43, No. 12, 01.12.2011, p. 1241-1246.

Research output: Contribution to journalArticle

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, M, Burns, JC, Burgner, D, Kuijpers, TW, Hibberd, ML, Lau, YL, Zhang, J, Ma, XJ, Liu, F, Wu, L, Yoo, JJ, Hong, SJ, Kim, KJ, Kim, JJ, Park, YM, Hong, YM, Sohn, S, Jang, G, Ha, KS, Nam, H-K, Byeon, JH, Yun, SW, Han, MK, Lee, KY, Hwang, JY, Rhim, JW, Song, MS, Lee, HD, Kim, DS, Lee, JM, Chang, JS, Tsai, FJ, Liang, CD, Chen, MR, Chi, H, Chiu, NC, Huang, FY, Chang, LY, Huang, LM, Kuo, HC, Huang, KP, Lee, ML, Hwang, B, Huang, YC, Lee, PC, Odam, M, Christiansen, FT, Witt, C, Goldwater, P, Curtis, N, Palasanthiran, P, Ziegler, J, Nissen, M, Nourse, C, Kuipers, IM, Ottenkamp, JJ, Geissler, J, Biezeveld, M, Tacke, C, Filippini, L, Brogan, P, Klein, N, Shah, V, Dillon, M, Booy, R, Shingadia, D, Bose, A, Mukasa, T, Tulloh, R, Michie, C, Newburger, JW, Baker, AL, Rowley, AH, Shulman, ST, Mason, W, Takahashi, M, Melish, ME, Tremoulet, AH, Viswanathan, A, Rochtchina, E, Attia, J, Scott, R, Holliday, E & Harrap, S 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
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 Dec 1;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 ; Burns, Jane C. ; Burgner, David ; Kuijpers, Taco W. ; Hibberd, Martin L. ; Lau, Yu Lung ; Zhang, Jing ; Ma, Xiao Jing ; Liu, Fang ; Wu, Lin ; Yoo, Jeong Jin ; Hong, Soo Jong ; Kim, Kwi Joo ; Kim, Jae Jung ; Park, Young Mi ; Hong, Young Mi ; Sohn, Sejung ; Jang, Giyoung ; Ha, Kee Soo ; Nam, Hyo-Kyoung ; Byeon, Jung Hye ; Yun, Sin Weon ; Han, Myung Ki ; Lee, Kyung Yil ; Hwang, Ja Young ; Rhim, Jung Woo ; Song, Min Seob ; Lee, Hyoung Doo ; Kim, Dong Soo ; Lee, Jae Moo ; Chang, Jeng Sheng ; Tsai, Fuu Jen ; Liang, Chi Di ; Chen, Ming Ren ; Chi, Hsin ; Chiu, Nan Chang ; Huang, Fu Yuan ; Chang, Luan Yin ; Huang, Li Min ; Kuo, Ho Chang ; Huang, Kao Pin ; Lee, Meng Luen ; Hwang, Betau ; Huang, Yhu Chering ; Lee, Pi Chang ; Odam, Miranda ; Christiansen, Frank T. ; Witt, Campbell ; Goldwater, Paul ; Curtis, Nigel ; Palasanthiran, Pamela ; Ziegler, John ; Nissen, Michael ; Nourse, Clare ; Kuipers, Irene M. ; Ottenkamp, Jaap J. ; Geissler, Judy ; Biezeveld, Maarten ; Tacke, Carline ; Filippini, Luc ; Brogan, Paul ; Klein, Nigel ; Shah, Vanita ; Dillon, Michael ; Booy, Robert ; Shingadia, Delane ; Bose, Anu ; Mukasa, Thomas ; Tulloh, Robert ; Michie, Colin ; Newburger, Jane W. ; Baker, Annette L. ; Rowley, Anne H. ; Shulman, Stanford T. ; Mason, Wilbert ; Takahashi, Masato ; Melish, Marian E. ; Tremoulet, Adriana H. ; Viswanathan, Ananth ; Rochtchina, Elena ; Attia, John ; Scott, Rodney ; Holliday, Elizabeth ; Harrap, Stephen. / 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.",
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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

AU - Burns, Jane C.

AU - Burgner, David

AU - Kuijpers, Taco W.

AU - Hibberd, Martin L.

AU - Lau, Yu Lung

AU - Zhang, Jing

AU - Ma, Xiao Jing

AU - Liu, Fang

AU - Wu, Lin

AU - Yoo, Jeong Jin

AU - Hong, Soo Jong

AU - Kim, Kwi Joo

AU - Kim, Jae Jung

AU - Park, Young Mi

AU - Hong, Young Mi

AU - Sohn, Sejung

AU - Jang, Giyoung

AU - Ha, Kee Soo

AU - Nam, Hyo-Kyoung

AU - Byeon, Jung Hye

AU - Yun, Sin Weon

AU - Han, Myung Ki

AU - Lee, Kyung Yil

AU - Hwang, Ja Young

AU - Rhim, Jung Woo

AU - Song, Min Seob

AU - Lee, Hyoung Doo

AU - Kim, Dong Soo

AU - Lee, Jae Moo

AU - Chang, Jeng Sheng

AU - Tsai, Fuu Jen

AU - Liang, Chi Di

AU - Chen, Ming Ren

AU - Chi, Hsin

AU - Chiu, Nan Chang

AU - Huang, Fu Yuan

AU - Chang, Luan Yin

AU - Huang, Li Min

AU - Kuo, Ho Chang

AU - Huang, Kao Pin

AU - Lee, Meng Luen

AU - Hwang, Betau

AU - Huang, Yhu Chering

AU - Lee, Pi Chang

AU - Odam, Miranda

AU - Christiansen, Frank T.

AU - Witt, Campbell

AU - Goldwater, Paul

AU - Curtis, Nigel

AU - Palasanthiran, Pamela

AU - Ziegler, John

AU - Nissen, Michael

AU - Nourse, Clare

AU - Kuipers, Irene M.

AU - Ottenkamp, Jaap J.

AU - Geissler, Judy

AU - Biezeveld, Maarten

AU - Tacke, Carline

AU - Filippini, Luc

AU - Brogan, Paul

AU - Klein, Nigel

AU - Shah, Vanita

AU - Dillon, Michael

AU - Booy, Robert

AU - Shingadia, Delane

AU - Bose, Anu

AU - Mukasa, Thomas

AU - Tulloh, Robert

AU - Michie, Colin

AU - Newburger, Jane W.

AU - Baker, Annette L.

AU - Rowley, Anne H.

AU - Shulman, Stanford T.

AU - Mason, Wilbert

AU - Takahashi, Masato

AU - Melish, Marian E.

AU - Tremoulet, Adriana H.

AU - Viswanathan, Ananth

AU - Rochtchina, Elena

AU - Attia, John

AU - Scott, Rodney

AU - Holliday, Elizabeth

AU - Harrap, Stephen

PY - 2011/12/1

Y1 - 2011/12/1

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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