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

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TitleGenome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease
AuthorsKhor, CC24 46
Davila, S24 46
Breunis, WB8 27
Lee, YC12
Shimizu, C18 20
Wright, VJ33
Yeung, RSM53
Tan, DEK24
Sim, KS24
Wang, JJ16 49
Wong, TY26 46 49
Pang, J24 46
Mitchell, P49
Cimaz, R21 40
Dahdah, N47
Cheung, YF17
Huang, GY45
Yang, W17
Park, IS32
Lee, JK32
Wu, JY12
Levin, M33
Burns, JC18 20
Burgner, D37 41
Kuijpers, TW8 27
Hibberd, ML24 46
Lau, YL17
Zhang, J17
Ma, XJ45
Liu, F45
Wu, L45
Yoo, JJ3
Hong, SJ3
Kim, KJ3
Kim, JJ32
Park, YM32
Hong, YM22
Sohn, S22
Jang, GY42
Ha, KS42
Nam, HK42
Byeon, JH42
Yun, SW28
Han, MK19
Lee, KY11
Hwang, JY11
Rhim, JW11
Song, MS14
Lee, HD31
Kim, DS23
Lee, JM23
Chang, JS5
Tsai, FJ10
Liang, CD54
Chen, MR15
Chi, H15
Chiu, NC15
Huang, FY15
Chang, LY43
Huang, LM43
Kuo, HC54
Huang, KP54
Lee, ML38
Hwang, B25
Huang, YC54
Lee, PC13
Odam, M32 41
Christiansen, FT41
Witt, C36
Goldwater, P29 39
Curtis, N32 37
Palasanthiran, P6
Ziegler, J6
Nissen, M7
Nourse, C7
Kuipers, IM8
Ottenkamp, JJ8
Geissler, J8
Biezeveld, M8
Tacke, C8
Filippini, L9
Brogan, P34
Klein, N34
Shah, V34
Dillon, M34
Booy, R35
Shingadia, D35
Bose, A35
Mukasa, T35
Tulloh, R52
Michie, C4
Newburger, JW51
Baker, AL51
Rowley, AH30
Shulman, ST30
Mason, W1
Takahashi, M1
Melish, ME50
Tremoulet, AH44
Viswanathan, A2
Rochtchina, E2
Attia, J16
Scott, R48
Holliday, E48
Harrap, S49
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
CitationNature Genetics, 2011, v. 43 n. 12, p. 1241-1246 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ng.981
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.
ISSN1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
DOIhttp://dx.doi.org/10.1038/ng.981
ISI Accession Number IDWOS:000297931400020
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.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorKhor, CC
dc.contributor.authorDavila, S
dc.contributor.authorBreunis, WB
dc.contributor.authorLee, YC
dc.contributor.authorShimizu, C
dc.contributor.authorWright, VJ
dc.contributor.authorYeung, RSM
dc.contributor.authorTan, DEK
dc.contributor.authorSim, KS
dc.contributor.authorWang, JJ
dc.contributor.authorWong, TY
dc.contributor.authorPang, J
dc.contributor.authorMitchell, P
dc.contributor.authorCimaz, R
dc.contributor.authorDahdah, N
dc.contributor.authorCheung, YF
dc.contributor.authorHuang, GY
dc.contributor.authorYang, W
dc.contributor.authorPark, IS
dc.contributor.authorLee, JK
dc.contributor.authorWu, JY
dc.contributor.authorLevin, M
dc.contributor.authorBurns, JC
dc.contributor.authorBurgner, D
dc.contributor.authorKuijpers, TW
dc.contributor.authorHibberd, ML
dc.contributor.authorLau, YL
dc.contributor.authorZhang, J
dc.contributor.authorMa, XJ
dc.contributor.authorLiu, F
dc.contributor.authorWu, L
dc.contributor.authorYoo, JJ
dc.contributor.authorHong, SJ
dc.contributor.authorKim, KJ
dc.contributor.authorKim, JJ
dc.contributor.authorPark, YM
dc.contributor.authorHong, YM
dc.contributor.authorSohn, S
dc.contributor.authorJang, GY
dc.contributor.authorHa, KS
dc.contributor.authorNam, HK
dc.contributor.authorByeon, JH
dc.contributor.authorYun, SW
dc.contributor.authorHan, MK
dc.contributor.authorLee, KY
dc.contributor.authorHwang, JY
dc.contributor.authorRhim, JW
dc.contributor.authorSong, MS
dc.contributor.authorLee, HD
dc.contributor.authorKim, DS
dc.contributor.authorLee, JM
dc.contributor.authorChang, JS
dc.contributor.authorTsai, FJ
dc.contributor.authorLiang, CD
dc.contributor.authorChen, MR
dc.contributor.authorChi, H
dc.contributor.authorChiu, NC
dc.contributor.authorHuang, FY
dc.contributor.authorChang, LY
dc.contributor.authorHuang, LM
dc.contributor.authorKuo, HC
dc.contributor.authorHuang, KP
dc.contributor.authorLee, ML
dc.contributor.authorHwang, B
dc.contributor.authorHuang, YC
dc.contributor.authorLee, PC
dc.contributor.authorOdam, M
dc.contributor.authorChristiansen, FT
dc.contributor.authorWitt, C
dc.contributor.authorGoldwater, P
dc.contributor.authorCurtis, N
dc.contributor.authorPalasanthiran, P
dc.contributor.authorZiegler, J
dc.contributor.authorNissen, M
dc.contributor.authorNourse, C
dc.contributor.authorKuipers, IM
dc.contributor.authorOttenkamp, JJ
dc.contributor.authorGeissler, J
dc.contributor.authorBiezeveld, M
dc.contributor.authorTacke, C
dc.contributor.authorFilippini, L
dc.contributor.authorBrogan, P
dc.contributor.authorKlein, N
dc.contributor.authorShah, V
dc.contributor.authorDillon, M
dc.contributor.authorBooy, R
dc.contributor.authorShingadia, D
dc.contributor.authorBose, A
dc.contributor.authorMukasa, T
dc.contributor.authorTulloh, R
dc.contributor.authorMichie, C
dc.contributor.authorNewburger, JW
dc.contributor.authorBaker, AL
dc.contributor.authorRowley, AH
dc.contributor.authorShulman, ST
dc.contributor.authorMason, W
dc.contributor.authorTakahashi, M
dc.contributor.authorMelish, ME
dc.contributor.authorTremoulet, AH
dc.contributor.authorViswanathan, A
dc.contributor.authorRochtchina, E
dc.contributor.authorAttia, J
dc.contributor.authorScott, R
dc.contributor.authorHolliday, E
dc.contributor.authorHarrap, S
dc.date.accessioned2012-07-16T09:48:39Z
dc.date.available2012-07-16T09:48:39Z
dc.date.issued2011
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationNature Genetics, 2011, v. 43 n. 12, p. 1241-1246 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ng.981
dc.identifier.citeulike10091441
dc.identifier.doihttp://dx.doi.org/10.1038/ng.981
dc.identifier.epage1246
dc.identifier.hkuros200816
dc.identifier.isiWOS:000297931400020
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.

dc.identifier.issn1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
dc.identifier.issue12
dc.identifier.pmid22081228
dc.identifier.scopuseid_2-s2.0-82255186670
dc.identifier.spage1241
dc.identifier.urihttp://hdl.handle.net/10722/152796
dc.identifier.volume43
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
dc.publisher.placeUnited States
dc.relation.ispartofNature Genetics
dc.relation.referencesReferences in Scopus
dc.titleGenome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease
dc.typeArticle
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. Academic Medical Centre, University of Amsterdam
  9. Juliana Children's Hospital
  10. China Medical University and Hospital
  11. Daejeon St. Mary's Hospital
  12. Academia Sinica Taiwan
  13. Veterans General Hospital-Taipei
  14. Inje University Paik Hospital
  15. Mackay Memorial Hospital Taiwan
  16. University of Sydney
  17. The University of Hong Kong
  18. Rady Children's Hospital
  19. Ulsan University
  20. University of California, San Diego, School of Medicine
  21. null
  22. Ewha Women's University, College of Medicine
  23. Yonsei University College of Medicine
  24. Genome Institute of Singapore
  25. Taipei City Hospital Taiwan
  26. Singapore National Eye Centre
  27. University of Amsterdam
  28. Chung-Ang University, College of Medicine
  29. University of Adelaide
  30. Northwestern University Feinberg School of Medicine
  31. Pusan National University, College of Medicine
  32. University of Ulsan, College of Medicine
  33. Imperial College London
  34. UCL Institute of Child Health
  35. null
  36. Royal Perth Hospital
  37. Royal Children's Hospital, Melbourne
  38. Changhua Christian Hospital Taiwan
  39. Women's and Children's Hospital Adelaide
  40. Università degli Studi di Firenze
  41. University of Western Australia
  42. Korea University
  43. National Taiwan University Hospital
  44. University of California, San Diego
  45. Fudan University
  46. National University of Singapore
  47. null
  48. Hunter Medical Research Institute, Australia
  49. University of Melbourne
  50. Kapliolani Children's Hospital
  51. Children's Hospital Boston
  52. University of Bristol
  53. Hospital for Sick Children, Toronto
  54. Chang Gung Memorial Hospital