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Article: A new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigrees

TitleA new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigrees
Authors
Issue Date2005
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.psychgenetics.com
Citation
Psychiatric Genetics, 2005, v. 15 n. 3, p. 181-187 How to Cite?
AbstractObjective: Although LOD score methods have been applied to diseases with complex modes of inheritance, linkage analysis of quantitative traits has tended to rely on non-parametric methods based on regression or variance components analysis. Here, we describe a new method for LOD score analysis of quantitative traits which does not require specification of a mode of inheritance. Methods: The technique is derived from the MFLINK method for dichotomous traits. A range of plausible transmission models is constructed, constrained to yield the correct population mean and variance for the trait but differing with respect to the contribution to the variance due to the locus under consideration. Maximized LOD scores under homogeneity and admixture are calculated, as is a model-free LOD score which compares the maximized likelihoods under admixture assuming linkage and no linkage. These LOD scores have known asymptotic distributions and hence can be used to provide a statistical test for linkage. The method has been implemented in a program called QMFLINK. It was applied to data sets simulated using a variety of transmission models and to a measure of monoamine oxidase activity in 105 pedigrees from the Collaborative Study on the Genetics of Alcoholism. Results: With the simulated data, the results showed that the new method could detect linkage well if the true allele frequency for the trait was close to that specified. However, it performed poorly on models in which the true allele frequency was much rarer. For the Collaborative Study on the Genetics of Alcoholism data set only a modest overlap was observed between the results obtained from the new method and those obtained when the same data were analysed previously using regression and variance components analysis. Of interest is that D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but did not indicate linkage using the previous methods. However, this region did produce evidence for linkage in a separate data set, suggesting that QMFLINK may have been able to detect a true linkage which was not picked up by the other methods. Conclusion: The application of model-free LOD score analysis to quantitative traits is novel and deserves further evaluation of its merits and disadvantages relative to other methods. © 2005 Lippincott Williams & Wilkins.
Persistent Identifierhttp://hdl.handle.net/10722/175939
ISSN
2015 Impact Factor: 1.736
2015 SCImago Journal Rankings: 0.968
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCurtis, Den_US
dc.contributor.authorKnight, Jen_US
dc.contributor.authorSham, PCen_US
dc.date.accessioned2012-11-26T09:02:40Z-
dc.date.available2012-11-26T09:02:40Z-
dc.date.issued2005en_US
dc.identifier.citationPsychiatric Genetics, 2005, v. 15 n. 3, p. 181-187en_US
dc.identifier.issn0955-8829en_US
dc.identifier.urihttp://hdl.handle.net/10722/175939-
dc.description.abstractObjective: Although LOD score methods have been applied to diseases with complex modes of inheritance, linkage analysis of quantitative traits has tended to rely on non-parametric methods based on regression or variance components analysis. Here, we describe a new method for LOD score analysis of quantitative traits which does not require specification of a mode of inheritance. Methods: The technique is derived from the MFLINK method for dichotomous traits. A range of plausible transmission models is constructed, constrained to yield the correct population mean and variance for the trait but differing with respect to the contribution to the variance due to the locus under consideration. Maximized LOD scores under homogeneity and admixture are calculated, as is a model-free LOD score which compares the maximized likelihoods under admixture assuming linkage and no linkage. These LOD scores have known asymptotic distributions and hence can be used to provide a statistical test for linkage. The method has been implemented in a program called QMFLINK. It was applied to data sets simulated using a variety of transmission models and to a measure of monoamine oxidase activity in 105 pedigrees from the Collaborative Study on the Genetics of Alcoholism. Results: With the simulated data, the results showed that the new method could detect linkage well if the true allele frequency for the trait was close to that specified. However, it performed poorly on models in which the true allele frequency was much rarer. For the Collaborative Study on the Genetics of Alcoholism data set only a modest overlap was observed between the results obtained from the new method and those obtained when the same data were analysed previously using regression and variance components analysis. Of interest is that D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but did not indicate linkage using the previous methods. However, this region did produce evidence for linkage in a separate data set, suggesting that QMFLINK may have been able to detect a true linkage which was not picked up by the other methods. Conclusion: The application of model-free LOD score analysis to quantitative traits is novel and deserves further evaluation of its merits and disadvantages relative to other methods. © 2005 Lippincott Williams & Wilkins.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.psychgenetics.comen_US
dc.relation.ispartofPsychiatric Geneticsen_US
dc.subject.meshAlcoholism - Geneticsen_US
dc.subject.meshAllelesen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Frequencyen_US
dc.subject.meshGenes, Dominanten_US
dc.subject.meshGenetic Heterogeneityen_US
dc.subject.meshGenetic Linkageen_US
dc.subject.meshHumansen_US
dc.subject.meshLod Scoreen_US
dc.subject.meshMaleen_US
dc.subject.meshMonoamine Oxidase - Geneticsen_US
dc.subject.meshPedigreeen_US
dc.subject.meshQuantitative Trait Locien_US
dc.titleA new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigreesen_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.doi10.1097/01.ypg.0000173119.04430.65en_US
dc.identifier.pmid16094252-
dc.identifier.scopuseid_2-s2.0-24144497177en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-24144497177&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume15en_US
dc.identifier.issue3en_US
dc.identifier.spage181en_US
dc.identifier.epage187en_US
dc.identifier.isiWOS:000231808400007-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCurtis, D=14633020700en_US
dc.identifier.scopusauthoridKnight, J=13002769800en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US

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