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Article: Joint linkage of multiple loci for a complex disorder

TitleJoint linkage of multiple loci for a complex disorder
Authors
Issue Date1993
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 1993, v. 53 n. 2, p. 353-366 How to Cite?
AbstractMany investigators who have been searching for linkage to complex diseases have by now accumulated a drawer full of negative results. If disease is actually caused by genes at several loci, these data might contain multiple- locus system (MLS) information that the investigator does not realize. Trying to obtain this information formally, through the MLS likelihood, leads to severe computational and statistical difficulties. Therefore, we propose a scheme of inference based on single-locus (SL) statistics, considered jointly. By simulation, we find that the MLS lod score is closely approximated by the sum of SL lod scores. However, we also find that for moderately large systems, say three or four loci, both MLS and SL lod scores are likely to be inconclusive. Nonetheless, MLS can often be detected through the correlation of individual pedigree SL lod scores. Significant correlation is itself evidence of an MLS, because, in the absence of linkage, false- positive lod scores are necessarily random. Under epistasis SL lod scores tend to be positively correlated among pedigrees, while under independent action SL lod scores from high-density samples tend to be negatively correlated.
Persistent Identifierhttp://hdl.handle.net/10722/175686
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMaclean, CJen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorKendler, KSen_US
dc.date.accessioned2012-11-26T09:00:30Z-
dc.date.available2012-11-26T09:00:30Z-
dc.date.issued1993en_US
dc.identifier.citationAmerican Journal Of Human Genetics, 1993, v. 53 n. 2, p. 353-366en_US
dc.identifier.issn0002-9297en_US
dc.identifier.urihttp://hdl.handle.net/10722/175686-
dc.description.abstractMany investigators who have been searching for linkage to complex diseases have by now accumulated a drawer full of negative results. If disease is actually caused by genes at several loci, these data might contain multiple- locus system (MLS) information that the investigator does not realize. Trying to obtain this information formally, through the MLS likelihood, leads to severe computational and statistical difficulties. Therefore, we propose a scheme of inference based on single-locus (SL) statistics, considered jointly. By simulation, we find that the MLS lod score is closely approximated by the sum of SL lod scores. However, we also find that for moderately large systems, say three or four loci, both MLS and SL lod scores are likely to be inconclusive. Nonetheless, MLS can often be detected through the correlation of individual pedigree SL lod scores. Significant correlation is itself evidence of an MLS, because, in the absence of linkage, false- positive lod scores are necessarily random. Under epistasis SL lod scores tend to be positively correlated among pedigrees, while under independent action SL lod scores from high-density samples tend to be negatively correlated.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.meshChi-Square Distributionen_US
dc.subject.meshComputer Simulationen_US
dc.subject.meshEpistasis, Geneticen_US
dc.subject.meshGenetic Diseases, Inborn - Geneticsen_US
dc.subject.meshGenetic Linkageen_US
dc.subject.meshGenetic Markersen_US
dc.subject.meshHumansen_US
dc.subject.meshLod Scoreen_US
dc.subject.meshModels, Geneticen_US
dc.subject.meshModels, Statisticalen_US
dc.subject.meshPedigreeen_US
dc.subject.meshReproducibility Of Resultsen_US
dc.titleJoint linkage of multiple loci for a complex disorderen_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.pmid8328454-
dc.identifier.scopuseid_2-s2.0-0027495139en_US
dc.identifier.volume53en_US
dc.identifier.issue2en_US
dc.identifier.spage353en_US
dc.identifier.epage366en_US
dc.identifier.isiWOS:A1993LN82000008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMacLean, CJ=7102972772en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridKendler, KS=35396760800en_US

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