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Article: Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations

TitleIdentifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations
Authors
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mp
Citation
Molecular Psychiatry, 2005, v. 10 n. 11, p. 1037-1044 How to Cite?
AbstractThe dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms (SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 (SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia. © 2005 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/175944
ISSN
2015 Impact Factor: 13.314
2015 SCImago Journal Rankings: 6.790
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Ten_US
dc.contributor.authorZhang, Fen_US
dc.contributor.authorLiu, Xen_US
dc.contributor.authorSun, Xen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorCrombie, Cen_US
dc.contributor.authorMa, Xen_US
dc.contributor.authorWang, Qen_US
dc.contributor.authorMeng, Hen_US
dc.contributor.authorDeng, Wen_US
dc.contributor.authorYates, Pen_US
dc.contributor.authorHu, Xen_US
dc.contributor.authorWalker, Nen_US
dc.contributor.authorMurray, RMen_US
dc.contributor.authorSt Clair, Den_US
dc.contributor.authorCollier, DAen_US
dc.date.accessioned2012-11-26T09:02:45Z-
dc.date.available2012-11-26T09:02:45Z-
dc.date.issued2005en_US
dc.identifier.citationMolecular Psychiatry, 2005, v. 10 n. 11, p. 1037-1044en_US
dc.identifier.issn1359-4184en_US
dc.identifier.urihttp://hdl.handle.net/10722/175944-
dc.description.abstractThe dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms (SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 (SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia. © 2005 Nature Publishing Group All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mpen_US
dc.relation.ispartofMolecular Psychiatryen_US
dc.subject.meshAllelesen_US
dc.subject.meshCarrier Proteins - Geneticsen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshChinaen_US
dc.subject.meshChromosomes, Human, Pair 6 - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Markersen_US
dc.subject.meshHaplotypesen_US
dc.subject.meshHumansen_US
dc.subject.meshLinkage Disequilibriumen_US
dc.subject.meshMaleen_US
dc.subject.meshPolymorphism, Single Nucleotideen_US
dc.subject.meshRisk Factorsen_US
dc.subject.meshSchizophrenia - Geneticsen_US
dc.subject.meshScotlanden_US
dc.titleIdentifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populationsen_US
dc.typeArticleen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.mp.4001718en_US
dc.identifier.pmid16044171-
dc.identifier.scopuseid_2-s2.0-27544484881en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-27544484881&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue11en_US
dc.identifier.spage1037en_US
dc.identifier.epage1044en_US
dc.identifier.isiWOS:000232833000010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLi, T=36072008200en_US
dc.identifier.scopusauthoridZhang, F=24465951900en_US
dc.identifier.scopusauthoridLiu, X=7409286408en_US
dc.identifier.scopusauthoridSun, X=7405624871en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridCrombie, C=12240136900en_US
dc.identifier.scopusauthoridMa, X=35354066000en_US
dc.identifier.scopusauthoridWang, Q=7406916913en_US
dc.identifier.scopusauthoridMeng, H=9133658800en_US
dc.identifier.scopusauthoridDeng, W=7202222559en_US
dc.identifier.scopusauthoridYates, P=8921964400en_US
dc.identifier.scopusauthoridHu, X=7404709241en_US
dc.identifier.scopusauthoridWalker, N=7201514664en_US
dc.identifier.scopusauthoridMurray, RM=35406239400en_US
dc.identifier.scopusauthoridSt Clair, D=35354078200en_US
dc.identifier.scopusauthoridCollier, DA=26642980600en_US
dc.identifier.citeulike265038-

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