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, MAR1
Sham, P2 3
Daly, MJ1 4
Purcell, S1 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
2011 Impact Factor: 2.52
2011 SCImago Journal Rankings: 0.169
DOIhttp://dx.doi.org/10.1007/s10519-007-9149-0
ISI Accession Number IDWOS:000247412000010
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 2.52
2011 SCImago Journal Rankings: 0.169
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
Author Affiliations
  1. Massachusetts General Hospital
  2. King's College London
  3. The University of Hong Kong
  4. Broad Institute