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Article: Ascertainment through family history of disease often decreases the power of family-based association studies

TitleAscertainment through family history of disease often decreases the power of family-based association studies
Authors
KeywordsAssociation
Complex disease
Family history
Power
Study design
TDT
Issue Date2007
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0001-8244
Citation
Behavior Genetics, 2007, v. 37 n. 4, p. 631-636 How to Cite?
AbstractSelection of cases with additional affected relatives has been shown to increase the power of the case-control association design. We investigated whether this strategy can also improve the power of family-based association studies that use the transmission disequilibrium test (TDT), while accounting for the effects of residual polygenic and environmental factors on disease liability. Ascertainment of parent-offspring trios conditional on the proband having affected first-degree relatives almost always reduced the power of the TDT. For many disease models, this reduction was quite considerable. In contrast, for the same sample size, designs that analyzed more than one affected offspring per family often improved power when compared to the standard parent-offspring trio design. Together, our results suggest that (1) residual polygenic and environmental influences should be considered when estimating the power of the TDT for studies that ascertain families with multiple affected relatives; (2) if trios are selected conditional on having additional affected offspring, then it is important to genotype and include in the analysis the additional siblings; (3) the ascertainment strategy should be considered when interpreting results from TDT analyses. Our analytic approach to estimate the asymptotic power of the TDT is implemented online at http://pngu.mgh.harvard. edu/∼purcell/gpc/. © 2007 Springer Science+Business Media, LLC.
Persistent Identifierhttp://hdl.handle.net/10722/81627
ISSN
2014 Impact Factor: 3.210
2014 SCImago Journal Rankings: 1.341
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorFerreira, MARen_HK
dc.contributor.authorSham, Pen_HK
dc.contributor.authorDaly, MJen_HK
dc.contributor.authorPurcell, Sen_HK
dc.date.accessioned2010-09-06T08:20:03Z-
dc.date.available2010-09-06T08:20:03Z-
dc.date.issued2007en_HK
dc.identifier.citationBehavior Genetics, 2007, v. 37 n. 4, p. 631-636en_HK
dc.identifier.issn0001-8244en_HK
dc.identifier.urihttp://hdl.handle.net/10722/81627-
dc.description.abstractSelection of cases with additional affected relatives has been shown to increase the power of the case-control association design. We investigated whether this strategy can also improve the power of family-based association studies that use the transmission disequilibrium test (TDT), while accounting for the effects of residual polygenic and environmental factors on disease liability. Ascertainment of parent-offspring trios conditional on the proband having affected first-degree relatives almost always reduced the power of the TDT. For many disease models, this reduction was quite considerable. In contrast, for the same sample size, designs that analyzed more than one affected offspring per family often improved power when compared to the standard parent-offspring trio design. Together, our results suggest that (1) residual polygenic and environmental influences should be considered when estimating the power of the TDT for studies that ascertain families with multiple affected relatives; (2) if trios are selected conditional on having additional affected offspring, then it is important to genotype and include in the analysis the additional siblings; (3) the ascertainment strategy should be considered when interpreting results from TDT analyses. Our analytic approach to estimate the asymptotic power of the TDT is implemented online at http://pngu.mgh.harvard. edu/∼purcell/gpc/. © 2007 Springer Science+Business Media, LLC.en_HK
dc.languageengen_HK
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0001-8244en_HK
dc.relation.ispartofBehavior Geneticsen_HK
dc.subjectAssociationen_HK
dc.subjectComplex diseaseen_HK
dc.subjectFamily historyen_HK
dc.subjectPoweren_HK
dc.subjectStudy designen_HK
dc.subjectTDTen_HK
dc.titleAscertainment through family history of disease often decreases the power of family-based association studiesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0001-8244&volume=37&spage=631&epage=636&date=2007&atitle=Ascertainment+through+family+history+of+disease+often+decreases+the+power+of+family-based+association+studies.en_HK
dc.identifier.emailSham, P: pcsham@hku.hken_HK
dc.identifier.authoritySham, P=rp00459en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s10519-007-9149-0en_HK
dc.identifier.pmid17372818en_HK
dc.identifier.scopuseid_2-s2.0-34250732224en_HK
dc.identifier.hkuros151799en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34250732224&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume37en_HK
dc.identifier.issue4en_HK
dc.identifier.spage631en_HK
dc.identifier.epage636en_HK
dc.identifier.isiWOS:000247412000010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridFerreira, MAR=9740452100en_HK
dc.identifier.scopusauthoridSham, P=34573429300en_HK
dc.identifier.scopusauthoridDaly, MJ=7201456226en_HK
dc.identifier.scopusauthoridPurcell, S=7005489464en_HK
dc.identifier.citeulike1537514-

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