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

TitleGenome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease
Authors
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
Citation
Nature Genetics, 2011, v. 43 n. 12, p. 1241-1246 How to Cite?
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. © 2011 Nature America, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/152796
ISSN
2013 Impact Factor: 29.648
2013 SCImago Journal Rankings: 24.052
ISI Accession Number ID
Funding AgencyGrant Number
Sainte-Justine Hospital research center
US National Institutes of Health, National Heart, Lung, Blood InstituteHL69413
National Heart Foundation of Australia
Agency for Science, Technology, and Research, Singapore
Ministry of Health & Welfare of the Republic of KoreaA010384
Shun Tak District Min Yuen Tong
Victorian Government
Funding Information:

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.

References

 

Author Affiliations
  1. Children's Hospital Los Angeles
  2. UCL
  3. Asan Medical Center
  4. Ealing Hospital
  5. Seoul Clinical Laboratories
  6. Sydney Children's Hospital
  7. University of Queensland
  8. Emma Kinderziekenhuis
  9. National University of Singapore, Faculty of Medicine
  10. Juliana Children's Hospital
  11. Yong Loo Lin School of Medicine
  12. Veterans General Hospital-Taipei
  13. Mackay Memorial Hospital Taiwan
  14. Inje University Paik Hospital
  15. The University of Hong Kong
  16. University of Sydney
  17. Daejeon St. Mary's Hospital
  18. China Medical University Hospital Taichung
  19. Rady Children's Hospital
  20. University of California, San Diego, School of Medicine
  21. Korea University Medical Center
  22. Ulsan University
  23. null
  24. Ewha Womans University School of Medicine
  25. Singapore National Eye Centre
  26. Yonsei University College of Medicine
  27. University of Amsterdam
  28. Genome Institute of Singapore
  29. Taipei City Hospital Taiwan
  30. University of Adelaide
  31. Pusan National University, College of Medicine
  32. Northwestern University Feinberg School of Medicine
  33. Chung-Ang University, College of Medicine
  34. Royal London Hospital
  35. Royal Children's Hospital, Melbourne
  36. UCL Institute of Child Health
  37. Royal Perth Hospital
  38. Women's and Children's Hospital Adelaide
  39. Università degli Studi di Firenze
  40. University of Western Australia
  41. University of Ulsan, College of Medicine
  42. Changhua Christian Hospital Taiwan
  43. Imperial College London
  44. National Taiwan University Hospital
  45. University of California, San Diego
  46. Fudan University
  47. National University of Singapore
  48. null
  49. Hunter Medical Research Institute, Australia
  50. University of Melbourne
  51. Hospital for Sick Children University of Toronto
  52. Children's Hospital Boston
  53. Institute of Biomedical Sciences Academia Sinica Taiwan
  54. University of Bristol
  55. Kapliolani Children's Hospital
  56. Chang Gung Memorial Hospital
  57. University of Queensland, School of Medical
DC FieldValueLanguage
dc.contributor.authorKhor, CCen_HK
dc.contributor.authorDavila, Sen_HK
dc.contributor.authorBreunis, WBen_HK
dc.contributor.authorLee, YCen_HK
dc.contributor.authorShimizu, Cen_HK
dc.contributor.authorWright, VJen_HK
dc.contributor.authorYeung, RSMen_HK
dc.contributor.authorTan, DEKen_HK
dc.contributor.authorSim, KSen_HK
dc.contributor.authorWang, JJen_HK
dc.contributor.authorWong, TYen_HK
dc.contributor.authorPang, Jen_HK
dc.contributor.authorMitchell, Pen_HK
dc.contributor.authorCimaz, Ren_HK
dc.contributor.authorDahdah, Nen_HK
dc.contributor.authorCheung, YFen_HK
dc.contributor.authorHuang, GYen_HK
dc.contributor.authorYang, Wen_HK
dc.contributor.authorPark, ISen_HK
dc.contributor.authorLee, JKen_HK
dc.contributor.authorWu, JYen_HK
dc.contributor.authorLevin, Men_HK
dc.contributor.authorBurns, JCen_HK
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dc.contributor.authorKuijpers, TWen_HK
dc.contributor.authorHibberd, MLen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorZhang, Jen_HK
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dc.contributor.authorLiu, Fen_HK
dc.contributor.authorWu, Len_HK
dc.contributor.authorYoo, JJen_HK
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dc.contributor.authorByeon, JHen_HK
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dc.contributor.authorHwang, JYen_HK
dc.contributor.authorRhim, JWen_HK
dc.contributor.authorSong, MSen_HK
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dc.contributor.authorKim, DSen_HK
dc.contributor.authorLee, JMen_HK
dc.contributor.authorChang, JSen_HK
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dc.contributor.authorFilippini, Len_HK
dc.contributor.authorBrogan, Pen_HK
dc.contributor.authorKlein, Nen_HK
dc.contributor.authorShah, Ven_HK
dc.contributor.authorDillon, Men_HK
dc.contributor.authorBooy, Ren_HK
dc.contributor.authorShingadia, Den_HK
dc.contributor.authorBose, Aen_HK
dc.contributor.authorMukasa, Ten_HK
dc.contributor.authorTulloh, Ren_HK
dc.contributor.authorMichie, Cen_HK
dc.contributor.authorNewburger, JWen_HK
dc.contributor.authorBaker, ALen_HK
dc.contributor.authorRowley, AHen_HK
dc.contributor.authorShulman, STen_HK
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dc.contributor.authorTakahashi, Men_HK
dc.contributor.authorMelish, MEen_HK
dc.contributor.authorTremoulet, AHen_HK
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dc.contributor.authorRochtchina, Een_HK
dc.contributor.authorAttia, Jen_HK
dc.contributor.authorScott, Ren_HK
dc.contributor.authorHolliday, Een_HK
dc.contributor.authorHarrap, Sen_HK
dc.date.accessioned2012-07-16T09:48:39Z-
dc.date.available2012-07-16T09:48:39Z-
dc.date.issued2011en_HK
dc.identifier.citationNature Genetics, 2011, v. 43 n. 12, p. 1241-1246en_HK
dc.identifier.issn1061-4036en_HK
dc.identifier.urihttp://hdl.handle.net/10722/152796-
dc.description.abstractKawasaki 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. © 2011 Nature America, Inc. All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.comen_HK
dc.relation.ispartofNature Geneticsen_HK
dc.titleGenome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki diseaseen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, YF:xfcheung@hku.hken_HK
dc.identifier.emailYang, W:yangwl@hkucc.hku.hken_HK
dc.identifier.emailLau, YL:lauylung@hkucc.hku.hken_HK
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dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ng.981en_HK
dc.identifier.pmid22081228en_HK
dc.identifier.scopuseid_2-s2.0-82255186670en_HK
dc.identifier.hkuros200816en_US
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dc.identifier.volume43en_HK
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dc.identifier.spage1241en_HK
dc.identifier.epage1246en_HK
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