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Article: Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2
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TitleGenome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2
 
AuthorsGarciaBarceló, MM1
Yeung, MY1
Miao, XP4
Tang, CSM1
Cheng, G
So, MT1
Ngan, ES1
Lui, VCH1
Chen, Y1
Liu, XL1
Hui, KJWS1
Li, L5
Guo, WH5
Sun, XB6
Tou, JF3
Chan, KW7
Wu, XZ2
Song, YQ1
Chan, D1
Cheung, K1
Chung, PHY1
Wong, KKY1
Sham, PC1 1
Cherny, SS1 1
Tam, PKH1
 
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/
 
CitationHuman Molecular Genetics, 2010, v. 19 n. 14, p. 2917-2925 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddq196
 
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.
 
ISSN0964-6906
2012 Impact Factor: 7.692
2012 SCImago Journal Rankings: 4.103
 
DOIhttp://dx.doi.org/10.1093/hmg/ddq196
 
PubMed Central IDPMC2893814
 
ISI Accession Number IDWOS:000279469100016
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.).

 
ReferencesReferences in Scopus
 
GrantsDevelopmental genomics and skeletal research
Study of the genetic basis of biliary atresia
 
DC FieldValue
dc.contributor.authorGarciaBarceló, MM
 
dc.contributor.authorYeung, MY
 
dc.contributor.authorMiao, XP
 
dc.contributor.authorTang, CSM
 
dc.contributor.authorCheng, G
 
dc.contributor.authorSo, MT
 
dc.contributor.authorNgan, ES
 
dc.contributor.authorLui, VCH
 
dc.contributor.authorChen, Y
 
dc.contributor.authorLiu, XL
 
dc.contributor.authorHui, KJWS
 
dc.contributor.authorLi, L
 
dc.contributor.authorGuo, WH
 
dc.contributor.authorSun, XB
 
dc.contributor.authorTou, JF
 
dc.contributor.authorChan, KW
 
dc.contributor.authorWu, XZ
 
dc.contributor.authorSong, YQ
 
dc.contributor.authorChan, D
 
dc.contributor.authorCheung, K
 
dc.contributor.authorChung, PHY
 
dc.contributor.authorWong, KKY
 
dc.contributor.authorSham, PC
 
dc.contributor.authorCherny, SS
 
dc.contributor.authorTam, PKH
 
dc.date.accessioned2010-09-17T10:41:14Z
 
dc.date.available2010-09-17T10:41:14Z
 
dc.date.issued2010
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationHuman Molecular Genetics, 2010, v. 19 n. 14, p. 2917-2925 [How to Cite?]
DOI: http://dx.doi.org/10.1093/hmg/ddq196
 
dc.identifier.citeulike7515522
 
dc.identifier.doihttp://dx.doi.org/10.1093/hmg/ddq196
 
dc.identifier.eissn1460-2083
 
dc.identifier.epage2925
 
dc.identifier.hkuros173123
 
dc.identifier.isiWOS:000279469100016
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.).

 
dc.identifier.issn0964-6906
2012 Impact Factor: 7.692
2012 SCImago Journal Rankings: 4.103
 
dc.identifier.issue14
 
dc.identifier.pmcidPMC2893814
 
dc.identifier.pmid20460270
 
dc.identifier.scopuseid_2-s2.0-77954530161
 
dc.identifier.spage2917
 
dc.identifier.urihttp://hdl.handle.net/10722/92275
 
dc.identifier.volume19
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofHuman Molecular Genetics
 
dc.relation.projectDevelopmental genomics and skeletal research
 
dc.relation.projectStudy of the genetic basis of biliary atresia
 
dc.relation.referencesReferences in Scopus
 
dc.subjectBile Duct Atresia
 
dc.subjectChromosome 10Q
 
dc.subjectControlled Study
 
dc.subjectFemale
 
dc.subjectGene Function
 
dc.subjectGene Identification
 
dc.subjectGene Locus
 
dc.subjectGenetic Association
 
dc.subjectGenetic Susceptibility
 
dc.subjectGenotype
 
dc.subjectHuman
 
dc.subjectMajor Clinical Study
 
dc.subjectMale
 
dc.subjectPriority Journal
 
dc.subjectRisk Factor
 
dc.subjectSingle Nucleotide Polymorphism
 
dc.titleGenome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Guiyang Medical College
  3. Zhejiang Children's Hospital
  4. Huazhong University of Science and Technology
  5. Beijing Children's Hospital
  6. Shandong University School of Medicine
  7. Chinese University of Hong Kong