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Article: Ascertainment through family history of disease often decreases the power of family-based association studies
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TitleAscertainment through family history of disease often decreases the power of family-based association studies
 
AuthorsFerreira, MAR2
Sham, P1 3
Daly, MJ2 4
Purcell, S2 4
 
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
 
CitationBehavior Genetics, 2007, v. 37 n. 4, p. 631-636 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s10519-007-9149-0
 
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.
 
ISSN0001-8244
2013 Impact Factor: 2.839
 
DOIhttp://dx.doi.org/10.1007/s10519-007-9149-0
 
ISI Accession Number IDWOS:000247412000010
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorFerreira, MAR
 
dc.contributor.authorSham, P
 
dc.contributor.authorDaly, MJ
 
dc.contributor.authorPurcell, S
 
dc.date.accessioned2010-09-06T08:20:03Z
 
dc.date.available2010-09-06T08:20:03Z
 
dc.date.issued2007
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationBehavior Genetics, 2007, v. 37 n. 4, p. 631-636 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s10519-007-9149-0
 
dc.identifier.citeulike1537514
 
dc.identifier.doihttp://dx.doi.org/10.1007/s10519-007-9149-0
 
dc.identifier.epage636
 
dc.identifier.hkuros151799
 
dc.identifier.isiWOS:000247412000010
 
dc.identifier.issn0001-8244
2013 Impact Factor: 2.839
 
dc.identifier.issue4
 
dc.identifier.openurl
 
dc.identifier.pmid17372818
 
dc.identifier.scopuseid_2-s2.0-34250732224
 
dc.identifier.spage631
 
dc.identifier.urihttp://hdl.handle.net/10722/81627
 
dc.identifier.volume37
 
dc.languageeng
 
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0001-8244
 
dc.publisher.placeUnited States
 
dc.relation.ispartofBehavior Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.subjectAssociation
 
dc.subjectComplex disease
 
dc.subjectFamily history
 
dc.subjectPower
 
dc.subjectStudy design
 
dc.subjectTDT
 
dc.titleAscertainment through family history of disease often decreases the power of family-based association studies
 
dc.typeArticle
 
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Author Affiliations
  1. King's College London
  2. Massachusetts General Hospital
  3. The University of Hong Kong
  4. Broad Institute