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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
Khor, CCDavila, SBreunis, WBLee, YCShimizu, CWright, VJYeung, RSMTan, DEKSim, KSWang, JJWong, TYPang, JMitchell, PCimaz, RDahdah, NCheung, YFHuang, GYYang, WPark, ISLee, JKWu, JYLevin, MBurns, JCBurgner, DKuijpers, TWHibberd, MLLau, YLZhang, JMa, XJLiu, FWu, LYoo, JJHong, SJKim, KJKim, JJPark, YMHong, YMSohn, SJang, GYHa, KSNam, HKByeon, JHYun, SWHan, MKLee, KYHwang, JYRhim, JWSong, MSLee, HDKim, DSLee, JMChang, JSTsai, FJLiang, CDChen, MRChi, HChiu, NCHuang, FYChang, LYHuang, LMKuo, HCHuang, KPLee, MLHwang, BHuang, YCLee, PCOdam, MChristiansen, FTWitt, CGoldwater, PCurtis, NPalasanthiran, PZiegler, JNissen, MNourse, CKuipers, IMOttenkamp, JJGeissler, JBiezeveld, MTacke, CFilippini, LBrogan, PKlein, NShah, VDillon, MBooy, RShingadia, DBose, AMukasa, TTulloh, RMichie, CNewburger, JWBaker, ALRowley, AHShulman, STMason, WTakahashi, MMelish, METremoulet, AHViswanathan, ARochtchina, EAttia, JScott, RHolliday, EHarrap, S
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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/152796
ISSN
1061-4036
2023 Impact Factor: 31.7
2023 SCImago Journal Rankings: 17.300
ISI Accession Number ID
WOS: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.

References
References in Scopus

 

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
dc.contributor.authorBurgner, Den_HK
dc.contributor.authorKuijpers, TWen_HK
dc.contributor.authorHibberd, MLen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorZhang, Jen_HK
dc.contributor.authorMa, XJen_HK
dc.contributor.authorLiu, Fen_HK
dc.contributor.authorWu, Len_HK
dc.contributor.authorYoo, JJen_HK
dc.contributor.authorHong, SJen_HK
dc.contributor.authorKim, KJen_HK
dc.contributor.authorKim, JJen_HK
dc.contributor.authorPark, YMen_HK
dc.contributor.authorHong, YMen_HK
dc.contributor.authorSohn, Sen_HK
dc.contributor.authorJang, GYen_HK
dc.contributor.authorHa, KSen_HK
dc.contributor.authorNam, HKen_HK
dc.contributor.authorByeon, JHen_HK
dc.contributor.authorYun, SWen_HK
dc.contributor.authorHan, MKen_HK
dc.contributor.authorLee, KYen_HK
dc.contributor.authorHwang, JYen_HK
dc.contributor.authorRhim, JWen_HK
dc.contributor.authorSong, MSen_HK
dc.contributor.authorLee, HDen_HK
dc.contributor.authorKim, DSen_HK
dc.contributor.authorLee, JMen_HK
dc.contributor.authorChang, JSen_HK
dc.contributor.authorTsai, FJen_HK
dc.contributor.authorLiang, CDen_HK
dc.contributor.authorChen, MRen_HK
dc.contributor.authorChi, Hen_HK
dc.contributor.authorChiu, NCen_HK
dc.contributor.authorHuang, FYen_HK
dc.contributor.authorChang, LYen_HK
dc.contributor.authorHuang, LMen_HK
dc.contributor.authorKuo, HCen_HK
dc.contributor.authorHuang, KPen_HK
dc.contributor.authorLee, MLen_HK
dc.contributor.authorHwang, Ben_HK
dc.contributor.authorHuang, YCen_HK
dc.contributor.authorLee, PCen_HK
dc.contributor.authorOdam, Men_HK
dc.contributor.authorChristiansen, FTen_HK
dc.contributor.authorWitt, Cen_HK
dc.contributor.authorGoldwater, Pen_HK
dc.contributor.authorCurtis, Nen_HK
dc.contributor.authorPalasanthiran, Pen_HK
dc.contributor.authorZiegler, Jen_HK
dc.contributor.authorNissen, Men_HK
dc.contributor.authorNourse, Cen_HK
dc.contributor.authorKuipers, IMen_HK
dc.contributor.authorOttenkamp, JJen_HK
dc.contributor.authorGeissler, Jen_HK
dc.contributor.authorBiezeveld, Men_HK
dc.contributor.authorTacke, Cen_HK
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
dc.contributor.authorMason, Wen_HK
dc.contributor.authorTakahashi, Men_HK
dc.contributor.authorMelish, MEen_HK
dc.contributor.authorTremoulet, AHen_HK
dc.contributor.authorViswanathan, Aen_HK
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
dc.identifier.authorityCheung, YF=rp00382en_HK
dc.identifier.authorityYang, W=rp00524en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ng.981en_HK
dc.identifier.pmid22081228-
dc.identifier.scopuseid_2-s2.0-82255186670en_HK
dc.identifier.hkuros200816en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-82255186670&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume43en_HK
dc.identifier.issue12en_HK
dc.identifier.spage1241en_HK
dc.identifier.epage1246en_HK
dc.identifier.eissn1546-1718-
dc.identifier.isiWOS:000297931400020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKhor, CC=13404065800en_HK
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dc.identifier.scopusauthoridLee, YC=36152950900en_HK
dc.identifier.scopusauthoridShimizu, C=7006192297en_HK
dc.identifier.scopusauthoridWright, VJ=36124332500en_HK
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dc.identifier.scopusauthoridTan, DEK=53880667400en_HK
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dc.identifier.scopusauthoridWang, JJ=35231432000en_HK
dc.identifier.scopusauthoridWong, TY=35231271400en_HK
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dc.identifier.citeulike10091441-
dc.identifier.issnl1061-4036-

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