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Article: Model-free linkage analysis using likelihoods

TitleModel-free linkage analysis using likelihoods
Authors
Issue Date1995
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 1995, v. 57 n. 3, p. 703-716 How to Cite?
AbstractMisspecification of transmission model parameters can produce artifactually negative lod scores at small recombination fractions and in multipoint analysis. To avoid this problem, we have tried to devise a test that aims to detect a genetic effect at a particular locus, rather than attempting to estimate the map position of a locus with specified effect. Maximizing likelihoods over transmission model parameters, as well as linkage parameters, can produce seriously biased parameter estimates and so yield tests that lack power for the detection of linkage. However, constraining the transmission model parameters to produce the correct population prevalence largely avoids this problem. For computational convenience, we recommend that the likelihoods under linkage and nonlinkage are independently maximized over a limited set of transmission models, ranging from Mendelian dominant to null effect and from null effect to Mendelian recessive. In order to test for a genetic effect at a given map position, the likelihood under linkage is maximized over admixture, the proportion of families linked. Application to simulated data for a wide range of transmission models in both affected sib pairs and pedigrees demonstrates that the new method is well behaved under the null hypothesis and provides a powerful test for linkage when it is present. This test requires no specification of transmission model parameters, apart from an approximate estimate of the population prevalence. It can be applied equally to sib pairs and pedigrees, and, since it does not diminish the lod score at test positions very close to a marker, it is suitable for application to multipoint data.
Persistent Identifierhttp://hdl.handle.net/10722/175731
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCurtis, Den_US
dc.contributor.authorSham, PCen_US
dc.date.accessioned2012-11-26T09:00:49Z-
dc.date.available2012-11-26T09:00:49Z-
dc.date.issued1995en_US
dc.identifier.citationAmerican Journal Of Human Genetics, 1995, v. 57 n. 3, p. 703-716en_US
dc.identifier.issn0002-9297en_US
dc.identifier.urihttp://hdl.handle.net/10722/175731-
dc.description.abstractMisspecification of transmission model parameters can produce artifactually negative lod scores at small recombination fractions and in multipoint analysis. To avoid this problem, we have tried to devise a test that aims to detect a genetic effect at a particular locus, rather than attempting to estimate the map position of a locus with specified effect. Maximizing likelihoods over transmission model parameters, as well as linkage parameters, can produce seriously biased parameter estimates and so yield tests that lack power for the detection of linkage. However, constraining the transmission model parameters to produce the correct population prevalence largely avoids this problem. For computational convenience, we recommend that the likelihoods under linkage and nonlinkage are independently maximized over a limited set of transmission models, ranging from Mendelian dominant to null effect and from null effect to Mendelian recessive. In order to test for a genetic effect at a given map position, the likelihood under linkage is maximized over admixture, the proportion of families linked. Application to simulated data for a wide range of transmission models in both affected sib pairs and pedigrees demonstrates that the new method is well behaved under the null hypothesis and provides a powerful test for linkage when it is present. This test requires no specification of transmission model parameters, apart from an approximate estimate of the population prevalence. It can be applied equally to sib pairs and pedigrees, and, since it does not diminish the lod score at test positions very close to a marker, it is suitable for application to multipoint data.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.subject.meshChromosome Mappingen_US
dc.subject.meshGenetic Linkageen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHumansen_US
dc.subject.meshLikelihood Functionsen_US
dc.subject.meshLod Scoreen_US
dc.subject.meshModels, Geneticen_US
dc.titleModel-free linkage analysis using likelihoodsen_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.pmid7668300-
dc.identifier.scopuseid_2-s2.0-0029096538en_US
dc.identifier.volume57en_US
dc.identifier.issue3en_US
dc.identifier.spage703en_US
dc.identifier.epage716en_US
dc.identifier.isiWOS:A1995RR60500021-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCurtis, D=14633020700en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US

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