Article: Parental phenotypes in family based association analysis

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TitleParental phenotypes in family based association analysis
AuthorsPurcell, S1 2
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
2011 Impact Factor: 10.603
2011 SCImago Journal Rankings: 2.479
DOIhttp://dx.doi.org/10.1086/427886
ISI Accession Number IDWOS:000226215100010
PubMed Central IDPMC1196370
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 10.603
2011 SCImago Journal Rankings: 2.479
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
Author Affiliations
  1. King's College London
  2. Whitehead Institute for Biomedical Research
  3. The University of Hong Kong