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 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, Gi Young 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

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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 - 2011 Dec

ASJC Scopus subject areas

  • Genetics

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    Khor, C. C., Davila, S., Breunis, W. B., Lee, Y. C., Shimizu, C., Wright, V. J., Yeung, R. S. M., Tan, D. E. K., Sim, K. S., Wang, J. J., Wong, T. Y., Pang, J., Mitchell, P., Cimaz, R., Dahdah, N., Cheung, Y. F., Huang, G. Y., Yang, W., Park, I. S., ... 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