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 SM Yeung, Dennis EK 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 Show all
Nature Genetics | NATURE PUBLISHING GROUP | Published : 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..View full abstract
Awarded by US National Institutes of Health, National Heart, Lung, Blood Institute
Awarded by Ministry of Health & Welfare of the Republic of Korea
Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
We thank all the individuals with Kawasaki disease and their families for participating in this study. We are grateful to W.-Y. Meah, H.-B. Toh, X. Chen, K.-K. Heng, C.-H. Wong, P.-L. Ng, S.H.Y. Chen and J.-W. Tay for technical assistance, to J. Pancheri, N. Innocentini, D. Donati and S. Fernandez for subject data collection and to D. Scherrer for laboratory assistance. The authors acknowledge the contributions of The Kawasaki Syndrome Support Group (UK) for their assistance in recruitment of the UK collection. This study makes use of data generated by the Wellcome Trust Case Control Consortium 2. A full list of the investigators who contributed to the generation of this data is available from the WTCCC2 website (see URLs). This work was funded in part by internal funding from the Sainte-Justine Hospital research center (awarded to N.D.), by grants from the US National Institutes of Health, National Heart, Lung, Blood Institute (HL69413, awarded to J.C.B.), from the National Heart Foundation of Australia (to D.B.) and by the Agency for Science, Technology, and Research, Singapore. The Korean Kawasaki Disease Genetics Consortium was supported by a grant from the Ministry of Health & Welfare of the Republic of Korea (A010384). The Hong Kong Kawasaki Disease Genetics Consortium was supported by the Shun Tak District Min Yuen Tong. The Australian research activity was partly supported by the Victorian Government's Operational Infrastructure Support Program.