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Article: Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity

TitleEvidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity
Authors
Issue Date1998
PublisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtl
Citation
Journal Of The American Medical Association, 1998, v. 280 n. 7, p. 614-618 How to Cite?
AbstractContext. - Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, and a recent study has suggested a locus on chromosome 12. Objective. - To confirm or refute the existence of a familial AD susceptibility locus on chromosome 12 in an independent sample of familial AD cases. Design. - Retrospective cohort study. DNA data for 6 chromosome 12 genetic markers were evaluated using parametric lod score and nonparametric linkage methods and linkage heterogeneity tests. The latter include the admixture test of homogeneity in the total group of families and the predivided sample test in families stratified by the presence or absence of an apolipoprotein E (APOE) ε4 allele among affected members. Parametric analyses were repeated assuming autosomal dominant inheritance of AD and either age- and sex-dependent penetrance or zero penetrance for the analysis of unaffected relatives. Setting. - Clinical populations in the continental United States, Canada, Argentina, and Italy. Patients. - Fifty-three white families composed of multiple members affected with AD, from whom DNA samples were obtained from 173 patients with AD whose conditions were diagnosed using established criteria and from 146 nondemented relatives. Main Outcome Measure. - Presence of an APOE ε4 allele among affected family members. Results. - Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families. However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1). The estimated proportion of linked families within the 53 families examined varied between 0.40 and 0.65, depending on the genetic model assumed and APOE status. The precise location of the AD gene could not be determined, but includes the entire region suggested previously. Nonparametric linkage analysis confirmed linkage to chromosome 12 with the strongest evidence at D12S96 (P<.001). Conclusions. - Our data provide independent confirmation of the existence of an AD susceptibility locus on chromosome 12 and suggest the existence of AD susceptibility genes on other chromosomes. Screening a larger set of families with additional chromosome markers will be necessary for identifying the chromosome 12 AD gene.
Persistent Identifierhttp://hdl.handle.net/10722/134749
ISSN
2015 Impact Factor: 37.684
2015 SCImago Journal Rankings: 6.440
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorRogaeva, Een_HK
dc.contributor.authorPremkumar, Sen_HK
dc.contributor.authorSong, Yen_HK
dc.contributor.authorSorbi, Sen_HK
dc.contributor.authorBrindle, Nen_HK
dc.contributor.authorPaterson, Aen_HK
dc.contributor.authorDuara, Ren_HK
dc.contributor.authorLevesque, Gen_HK
dc.contributor.authorYu, Gen_HK
dc.contributor.authorNishimura, Men_HK
dc.contributor.authorIkeda, Men_HK
dc.contributor.authorO'Toole, Cen_HK
dc.contributor.authorKawarai, Ten_HK
dc.contributor.authorJorge, Ren_HK
dc.contributor.authorVilarino, Den_HK
dc.contributor.authorBruni, ACen_HK
dc.contributor.authorFarrer, LAen_HK
dc.contributor.authorSt GeorgeHyslop, PHen_HK
dc.date.accessioned2011-07-14T07:02:38Z-
dc.date.available2011-07-14T07:02:38Z-
dc.date.issued1998en_HK
dc.identifier.citationJournal Of The American Medical Association, 1998, v. 280 n. 7, p. 614-618en_HK
dc.identifier.issn0098-7484en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134749-
dc.description.abstractContext. - Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, and a recent study has suggested a locus on chromosome 12. Objective. - To confirm or refute the existence of a familial AD susceptibility locus on chromosome 12 in an independent sample of familial AD cases. Design. - Retrospective cohort study. DNA data for 6 chromosome 12 genetic markers were evaluated using parametric lod score and nonparametric linkage methods and linkage heterogeneity tests. The latter include the admixture test of homogeneity in the total group of families and the predivided sample test in families stratified by the presence or absence of an apolipoprotein E (APOE) ε4 allele among affected members. Parametric analyses were repeated assuming autosomal dominant inheritance of AD and either age- and sex-dependent penetrance or zero penetrance for the analysis of unaffected relatives. Setting. - Clinical populations in the continental United States, Canada, Argentina, and Italy. Patients. - Fifty-three white families composed of multiple members affected with AD, from whom DNA samples were obtained from 173 patients with AD whose conditions were diagnosed using established criteria and from 146 nondemented relatives. Main Outcome Measure. - Presence of an APOE ε4 allele among affected family members. Results. - Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families. However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1). The estimated proportion of linked families within the 53 families examined varied between 0.40 and 0.65, depending on the genetic model assumed and APOE status. The precise location of the AD gene could not be determined, but includes the entire region suggested previously. Nonparametric linkage analysis confirmed linkage to chromosome 12 with the strongest evidence at D12S96 (P<.001). Conclusions. - Our data provide independent confirmation of the existence of an AD susceptibility locus on chromosome 12 and suggest the existence of AD susceptibility genes on other chromosomes. Screening a larger set of families with additional chromosome markers will be necessary for identifying the chromosome 12 AD gene.en_HK
dc.publisherAmerican Medical Association. The Journal's web site is located at http://jama.ama-assn.org/index.dtlen_HK
dc.relation.ispartofJournal of the American Medical Associationen_HK
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAged, 80 and overen_US
dc.subject.meshAlzheimer Disease/*geneticsen_US
dc.subject.meshApolipoproteins E/geneticsen_US
dc.subject.meshChromosome Mappingen_US
dc.subject.meshChromosomes, Human, Pair 12/*geneticsen_US
dc.subject.meshDNA/analysisen_US
dc.subject.meshFemaleen_US
dc.subject.mesh*Genetic Linkageen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHumansen_US
dc.subject.meshLod Scoreen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshModels, Statisticalen_US
dc.subject.meshPedigreeen_US
dc.subject.meshRetrospective Studiesen_US
dc.titleEvidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneityen_HK
dc.typeArticleen_HK
dc.identifier.emailSong, Y:songy@hkucc.hku.hken_HK
dc.identifier.authoritySong, Y=rp00488en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1001/jama.280.7.614en_HK
dc.identifier.pmid9718052-
dc.identifier.scopuseid_2-s2.0-0032547369en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032547369&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume280en_HK
dc.identifier.issue7en_HK
dc.identifier.spage614en_HK
dc.identifier.epage618en_HK
dc.identifier.isiWOS:000075384300029-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridRogaeva, E=35372614800en_HK
dc.identifier.scopusauthoridPremkumar, S=6603080131en_HK
dc.identifier.scopusauthoridSong, Y=7404921212en_HK
dc.identifier.scopusauthoridSorbi, S=7004417453en_HK
dc.identifier.scopusauthoridBrindle, N=7004637236en_HK
dc.identifier.scopusauthoridPaterson, A=7202360951en_HK
dc.identifier.scopusauthoridDuara, R=7005297173en_HK
dc.identifier.scopusauthoridLevesque, G=7006678462en_HK
dc.identifier.scopusauthoridYu, G=35370376900en_HK
dc.identifier.scopusauthoridNishimura, M=35503879100en_HK
dc.identifier.scopusauthoridIkeda, M=7404692203en_HK
dc.identifier.scopusauthoridO'Toole, C=7005035010en_HK
dc.identifier.scopusauthoridKawarai, T=34570127300en_HK
dc.identifier.scopusauthoridJorge, R=35275543900en_HK
dc.identifier.scopusauthoridVilarino, D=36832008700en_HK
dc.identifier.scopusauthoridBruni, AC=34567765200en_HK
dc.identifier.scopusauthoridFarrer, LA=7005139839en_HK
dc.identifier.scopusauthoridSt GeorgeHyslop, PH=7005637468en_HK

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