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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, CC28 47 9
Davila, S28 47
Breunis, WB8 27
Lee, YC53
Shimizu, C19 20
Wright, VJ43
Yeung, RSM51
Tan, DEK28
Sim, KS28
Wang, JJ50 16
Wong, TY11 25 50
Pang, J28 9
Mitchell, P50
Cimaz, R23 39
Dahdah, N48
Cheung, YF15
Huang, GY46
Yang, W15
Park, IS41
Lee, JK41
Wu, JY53
Levin, M43
Burns, JC19 20
Burgner, D40 35
Kuijpers, TW8 27
Hibberd, ML28 9
Lau, YL15
Zhang, J15
Ma, XJ46
Liu, F46
Wu, L46
Yoo, JJ3
Hong, SJ3
Kim, KJ3
Kim, JJ41
Park, YM41
Hong, YM24
Sohn, S24
Jang, GY21
Ha, KS21
Nam, HK21
Byeon, JH21
Yun, SW33
Han, MK22
Lee, KY17
Hwang, JY17
Rhim, JW17
Song, MS14
Lee, HD31
Kim, DS26
Lee, JM26
Chang, JS5
Tsai, FJ18
Liang, CD56
Chen, MR13
Chi, H13
Chiu, NC13
Huang, FY13
Chang, LY44
Huang, LM44
Kuo, HC56
Huang, KP56
Lee, ML42
Hwang, B29
Huang, YC56
Lee, PC12
Odam, M41 40
Christiansen, FT40
Witt, C37
Goldwater, P38 30
Curtis, N41 35
Palasanthiran, P6
Ziegler, J6
Nissen, M57
Nourse, C7
Kuipers, IM8
Ottenkamp, JJ8
Geissler, J8
Biezeveld, M8
Tacke, C8
Filippini, L10
Brogan, P36
Klein, N36
Shah, V36
Dillon, M36
Booy, R34
Shingadia, D34
Bose, A34
Mukasa, T34
Tulloh, R54
Michie, C4
Newburger, JW52
Baker, AL52
Rowley, AH32
Shulman, ST32
Mason, W1
Takahashi, M1
Melish, ME55
Tremoulet, AH45
Viswanathan, A2
Rochtchina, E2
Attia, J16
Scott, R49
Holliday, E49
Harrap, S50
 
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
2013 Impact Factor: 29.648
2013 SCImago Journal Rankings: 24.052
 
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 FieldValue
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.eissn1546-1718
 
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
2013 Impact Factor: 29.648
2013 SCImago Journal Rankings: 24.052
 
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
 
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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