Article: Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2

TitleGenome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2
Authors
KeywordsBile Duct Atresia
Chromosome 10Q
Controlled Study
Female
Gene Function
Gene Identification
Gene Locus
Genetic Association
Genetic Susceptibility
Genotype
Human
Major Clinical Study
Male
Priority Journal
Risk Factor
Single Nucleotide Polymorphism
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2010, v. 19 n. 14, p. 2917-2925 How to Cite?
AbstractBiliary atresia (BA) is characterized by the progressive fibrosclerosing obliteration of the extrahepatic biliary system during the first few weeks of life. Despite early diagnosis and prompt surgical intervention, the disease progresses to cirrhosis in many patients. The current theory for the pathogenesis of BA proposes that during the perinatal period, a still unknown exogenous factor meets the innate immune system of a genetically predisposed individual and induces an uncontrollable and potentially self-limiting immune response, which becomes manifest in liver fibrosis and atresia of the extrahepatic bile ducts. Genetic factors that could account for the disease, let alone for its high incidence in Chinese, are to be investigated. To identify BA susceptibility loci, we carried out a genome-wide association study (GWAS) using the Affymetrix 5.0 and 500 K marker sets. We genotyped nearly 500 000 single-nucleotide polymorphisms (SNPs) in 200 Chinese BA patients and 481 ethnically matched control subjects. The 10 most BA-associated SNPs from the GWAS were genotyped in an independent set of 124 BA and 90 control subjects. The strongest overall association was found for rs17095355 on 10q24, downstream XPNPEP1, a gene involved in the metabolism of inflammatory mediators. Allelic chi-square test P-value for the meta-analysis of the GWAS and replication results was 6.94 × 10-9. The identification of putative BA susceptibility loci not only opens new fields of investigation into the mechanisms underlying BA but may also provide new clues for the development of preventive and curative strategies. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.
Persistent Identifierhttp://hdl.handle.net/10722/92275
ISSN
2014 Impact Factor: 6.393
2014 SCImago Journal Rankings: 3.760
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 7628/06M
Seed Funding Programme for Basic Research200511159030
University Grants Committee of Hong KongAoE/M-04/04
National Institutes of HealthEY-12562
AOSPINEAOSBRC-07-02
Funding Information:

This work was supported by the Hong Kong Research Grants Council (HKU 7628/06M to P. K.-H. T.); and the Seed Funding Programme for Basic Research (200511159030 to P. K.-H. T.). Support was also received from the University Grants Committee of Hong Kong (AoE/M-04/04); the National Institutes of Health (EY-12562 to S. S. C. and P. C. S.), and AOSPINE (AOSBRC-07-02 to D. C.).

References
Grants
Errata

 

DC FieldValueLanguage
dc.contributor.authorGarciaBarceló, MMen_HK
dc.contributor.authorYeung, MYen_HK
dc.contributor.authorMiao, XPen_HK
dc.contributor.authorTang, CSMen_HK
dc.contributor.authorCheng, Gen_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorNgan, ESen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorLiu, XLen_HK
dc.contributor.authorHui, KJWSen_HK
dc.contributor.authorLi, Len_HK
dc.contributor.authorGuo, WHen_HK
dc.contributor.authorSun, XBen_HK
dc.contributor.authorTou, JFen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorWu, XZen_HK
dc.contributor.authorSong, YQen_HK
dc.contributor.authorChan, Den_HK
dc.contributor.authorCheung, Ken_HK
dc.contributor.authorChung, HYen_HK
dc.contributor.authorWong, KKYen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-17T10:41:14Z-
dc.date.available2010-09-17T10:41:14Z-
dc.date.issued2010en_HK
dc.identifier.citationHuman Molecular Genetics, 2010, v. 19 n. 14, p. 2917-2925en_HK
dc.identifier.issn0964-6906en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92275-
dc.description.abstractBiliary atresia (BA) is characterized by the progressive fibrosclerosing obliteration of the extrahepatic biliary system during the first few weeks of life. Despite early diagnosis and prompt surgical intervention, the disease progresses to cirrhosis in many patients. The current theory for the pathogenesis of BA proposes that during the perinatal period, a still unknown exogenous factor meets the innate immune system of a genetically predisposed individual and induces an uncontrollable and potentially self-limiting immune response, which becomes manifest in liver fibrosis and atresia of the extrahepatic bile ducts. Genetic factors that could account for the disease, let alone for its high incidence in Chinese, are to be investigated. To identify BA susceptibility loci, we carried out a genome-wide association study (GWAS) using the Affymetrix 5.0 and 500 K marker sets. We genotyped nearly 500 000 single-nucleotide polymorphisms (SNPs) in 200 Chinese BA patients and 481 ethnically matched control subjects. The 10 most BA-associated SNPs from the GWAS were genotyped in an independent set of 124 BA and 90 control subjects. The strongest overall association was found for rs17095355 on 10q24, downstream XPNPEP1, a gene involved in the metabolism of inflammatory mediators. Allelic chi-square test P-value for the meta-analysis of the GWAS and replication results was 6.94 × 10-9. The identification of putative BA susceptibility loci not only opens new fields of investigation into the mechanisms underlying BA but may also provide new clues for the development of preventive and curative strategies. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Molecular Geneticsen_HK
dc.subjectBile Duct Atresiaen_HK
dc.subjectChromosome 10Qen_HK
dc.subjectControlled Studyen_HK
dc.subjectFemaleen_HK
dc.subjectGene Functionen_HK
dc.subjectGene Identificationen_HK
dc.subjectGene Locusen_HK
dc.subjectGenetic Associationen_HK
dc.subjectGenetic Susceptibilityen_HK
dc.subjectGenotypeen_HK
dc.subjectHumanen_HK
dc.subjectMajor Clinical Studyen_HK
dc.subjectMaleen_HK
dc.subjectPriority Journalen_HK
dc.subjectRisk Factoren_HK
dc.subjectSingle Nucleotide Polymorphismen_HK
dc.titleGenome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2en_HK
dc.typeArticleen_HK
dc.identifier.emailGarciaBarceló, MM: mmgarcia@hku.hken_HK
dc.identifier.emailNgan, ES: engan@hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hku.hken_HK
dc.identifier.emailChen, Y: ychenc@hku.hken_HK
dc.identifier.emailSong, YQ: songy@hku.hken_HK
dc.identifier.emailChan, D: chand@hku.hken_HK
dc.identifier.emailCheung, K: cheungmc@hku.hken_HK
dc.identifier.emailWong, KKY: kkywong@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hku.hken_HK
dc.identifier.authorityGarciaBarceló, MM=rp00445en_HK
dc.identifier.authorityNgan, ES=rp00422en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityChen, Y=rp01318en_HK
dc.identifier.authoritySong, YQ=rp00488en_HK
dc.identifier.authorityChan, D=rp00540en_HK
dc.identifier.authorityCheung, K=rp00387en_HK
dc.identifier.authorityWong, KKY=rp01392en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/hmg/ddq196en_HK
dc.identifier.pmid20460270-
dc.identifier.pmcidPMC2893814-
dc.identifier.scopuseid_2-s2.0-77954530161en_HK
dc.identifier.hkuros173123-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954530161&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue14en_HK
dc.identifier.spage2917en_HK
dc.identifier.epage2925en_HK
dc.identifier.eissn1460-2083-
dc.identifier.isiWOS:000279469100016-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.erratumdoi:10.1093/hmg/ddq540-
dc.relation.projectDevelopmental genomics and skeletal research-
dc.relation.projectStudy of the genetic basis of biliary atresia-
dc.identifier.scopusauthoridGarciaBarceló, MM=6701767303en_HK
dc.identifier.scopusauthoridYeung, MY=16029841800en_HK
dc.identifier.scopusauthoridMiao, XP=7102585391en_HK
dc.identifier.scopusauthoridTang, CSM=35764635500en_HK
dc.identifier.scopusauthoridChen, G=36551966800en_HK
dc.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridNgan, ES=22234827500en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridChen, Y=36463185300en_HK
dc.identifier.scopusauthoridLiu, XL=36106291400en_HK
dc.identifier.scopusauthoridHui, KJWS=35764515100en_HK
dc.identifier.scopusauthoridLi, L=7501448457en_HK
dc.identifier.scopusauthoridGuo, WH=35285430300en_HK
dc.identifier.scopusauthoridSun, XB=36811242200en_HK
dc.identifier.scopusauthoridTou, JF=7006759358en_HK
dc.identifier.scopusauthoridChan, KW=15030099800en_HK
dc.identifier.scopusauthoridWu, XZ=36553563000en_HK
dc.identifier.scopusauthoridSong, YQ=7404921212en_HK
dc.identifier.scopusauthoridChan, D=7402216545en_HK
dc.identifier.scopusauthoridCheung, K=7402406754en_HK
dc.identifier.scopusauthoridChung, PHY=34568741300en_HK
dc.identifier.scopusauthoridWong, KKY=24438686400en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.citeulike7515522-

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