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Article: Parental phenotypes in family based association analysis
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TitleParental phenotypes in family based association analysis
 
AuthorsPurcell, S2 1
Sham, P1 3
Daly, MJ2
 
Issue Date2005
 
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
 
CitationAmerican Journal Of Human Genetics, 2005, v. 76 n. 2, p. 249-259 [How to Cite?]
DOI: http://dx.doi.org/10.1086/427886
 
AbstractFamily-based association designs are popular, because they offer inherent control of population stratification based on age, sex, ethnicity, and environmental exposure. However, the efficiency of these designs is hampered by current analytic strategies that consider only offspring phenotypes. Here, we describe the incorporation of parental phenotypes and, specifically, the inclusion of parental genotype-phenotype correlation terms in association tests, providing a series of tests that effectively span an efficiency-robustness spectrum. The model is based on the between-within-sibship association model presented in 1999 by Fulker and colleagues for quantitative traits and extended here to nuclear families. By use of a liability-threshold-model approach, standard dichotomous and/or qualitative disease phenotypes can be analyzed (and can include appropriate corrections for phenotypically ascertained samples), which allows for the application of this model to analysis of the commonly used affected-proband trio design. We show that the incorporation of parental phenotypes can considerably increase power, as compared with the standard transmission/disequilibrium test and equivalent quantitative tests, while providing both significant protection against stratification and a means of evaluating the contribution of stratification to positive results. This methodology enables the extraction of more information from existing family-based collections that are currently being genotyped and analyzed by use of standard approaches.
 
ISSN0002-9297
2013 Impact Factor: 10.987
 
DOIhttp://dx.doi.org/10.1086/427886
 
PubMed Central IDPMC1196370
 
ISI Accession Number IDWOS:000226215100010
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorPurcell, S
 
dc.contributor.authorSham, P
 
dc.contributor.authorDaly, MJ
 
dc.date.accessioned2007-10-30T06:22:13Z
 
dc.date.available2007-10-30T06:22:13Z
 
dc.date.issued2005
 
dc.description.abstractFamily-based association designs are popular, because they offer inherent control of population stratification based on age, sex, ethnicity, and environmental exposure. However, the efficiency of these designs is hampered by current analytic strategies that consider only offspring phenotypes. Here, we describe the incorporation of parental phenotypes and, specifically, the inclusion of parental genotype-phenotype correlation terms in association tests, providing a series of tests that effectively span an efficiency-robustness spectrum. The model is based on the between-within-sibship association model presented in 1999 by Fulker and colleagues for quantitative traits and extended here to nuclear families. By use of a liability-threshold-model approach, standard dichotomous and/or qualitative disease phenotypes can be analyzed (and can include appropriate corrections for phenotypically ascertained samples), which allows for the application of this model to analysis of the commonly used affected-proband trio design. We show that the incorporation of parental phenotypes can considerably increase power, as compared with the standard transmission/disequilibrium test and equivalent quantitative tests, while providing both significant protection against stratification and a means of evaluating the contribution of stratification to positive results. This methodology enables the extraction of more information from existing family-based collections that are currently being genotyped and analyzed by use of standard approaches.
 
dc.description.naturepublished_or_final_version
 
dc.format.extent158409 bytes
 
dc.format.extent593678 bytes
 
dc.format.mimetypeapplication/pdf
 
dc.format.mimetypeapplication/pdf
 
dc.identifier.citationAmerican Journal Of Human Genetics, 2005, v. 76 n. 2, p. 249-259 [How to Cite?]
DOI: http://dx.doi.org/10.1086/427886
 
dc.identifier.doihttp://dx.doi.org/10.1086/427886
 
dc.identifier.epage259
 
dc.identifier.isiWOS:000226215100010
 
dc.identifier.issn0002-9297
2013 Impact Factor: 10.987
 
dc.identifier.issue2
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC1196370
 
dc.identifier.pmid15614722
 
dc.identifier.scopuseid_2-s2.0-12344261638
 
dc.identifier.spage249
 
dc.identifier.urihttp://hdl.handle.net/10722/45299
 
dc.identifier.volume76
 
dc.languageeng
 
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofAmerican Journal of Human Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.rightsAmerican Journal of Human Genetics. Copyright © University of Chicago Press.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshGenetic Predisposition to Disease
 
dc.subject.meshModels, Genetic
 
dc.subject.meshPhenotype
 
dc.subject.meshGenotype
 
dc.subject.meshQuantitative Trait, Heritable
 
dc.titleParental phenotypes in family based association analysis
 
dc.typeArticle
 
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Author Affiliations
  1. King's College London
  2. Whitehead Institute for Biomedical Research
  3. The University of Hong Kong