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Article: Parental phenotypes in family based association analysis

TitleParental phenotypes in family based association analysis
Authors
Issue Date2005
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2005, v. 76 n. 2, p. 249-259 How to Cite?
Abstract
Family-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.
Persistent Identifierhttp://hdl.handle.net/10722/45299
ISSN
2013 Impact Factor: 10.987
PubMed Central ID
ISI Accession Number ID
References

 

Author Affiliations
  1. King's College London
  2. Whitehead Institute for Biomedical Research
  3. The University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorPurcell, Sen_HK
dc.contributor.authorSham, Pen_HK
dc.contributor.authorDaly, MJen_HK
dc.date.accessioned2007-10-30T06:22:13Z-
dc.date.available2007-10-30T06:22:13Z-
dc.date.issued2005en_HK
dc.identifier.citationAmerican Journal Of Human Genetics, 2005, v. 76 n. 2, p. 249-259en_HK
dc.identifier.issn0002-9297en_HK
dc.identifier.urihttp://hdl.handle.net/10722/45299-
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.en_HK
dc.format.extent158409 bytes-
dc.format.extent593678 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/pdf-
dc.languageengen_HK
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_HK
dc.relation.ispartofAmerican Journal of Human Geneticsen_HK
dc.rightsAmerican Journal of Human Genetics. Copyright © University of Chicago Press.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshGenetic Predisposition to Diseaseen_HK
dc.subject.meshModels, Geneticen_HK
dc.subject.meshPhenotypeen_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshQuantitative Trait, Heritableen_HK
dc.titleParental phenotypes in family based association analysisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9297&volume=76&issue=2&spage=249&epage=259&date=2005&atitle=Parental+phenotypes+in+family-based+association+analysisen_HK
dc.identifier.emailSham, P: pcsham@hku.hken_HK
dc.identifier.authoritySham, P=rp00459en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1086/427886en_HK
dc.identifier.pmid15614722en_HK
dc.identifier.pmcidPMC1196370-
dc.identifier.scopuseid_2-s2.0-12344261638en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-12344261638&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume76en_HK
dc.identifier.issue2en_HK
dc.identifier.spage249en_HK
dc.identifier.epage259en_HK
dc.identifier.isiWOS:000226215100010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridPurcell, S=7005489464en_HK
dc.identifier.scopusauthoridSham, P=34573429300en_HK
dc.identifier.scopusauthoridDaly, MJ=7201456226en_HK

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