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Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test

Wicks, J

Description

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, T(sp), which is also based on...[Show more]

dc.contributor.authorWicks, J
dc.date.accessioned2015-12-07T22:38:54Z
dc.identifier.issn0002-9297
dc.identifier.urihttp://hdl.handle.net/1885/23628
dc.description.abstractThe transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, T(sp), which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and T(sp) are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of 'TDT-like' statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent - and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs.
dc.publisherUniversity of Chicago Press
dc.sourceAmerican Journal of Human Genetics
dc.subjectKeywords: allele; article; family study; gene linkage disequilibrium; mathematical analysis; pedigree; priority journal; Alleles; Chromosome Mapping; False Positive Reactions; Female; Genes, Dominant; Genes, Recessive; Genetic Markers; Humans; Linkage Disequilibriu
dc.titleExploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume66
dc.date.issued2000
local.identifier.absfor160102 - Biological (Physical) Anthropology
local.identifier.ariespublicationMigratedxPub28
local.type.statusPublished Version
local.contributor.affiliationWicks, J, College of Physical and Mathematical Sciences, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage2005
local.bibliographicCitation.lastpage2008
local.identifier.doi10.1086/302912
dc.date.updated2015-12-07T10:42:43Z
local.identifier.scopusID2-s2.0-0033911953
CollectionsANU Research Publications

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