USE OF SIBLINGS AS CONTROLS IN CASE-CONTROL ASSOCIATION STUDIES

Authors
Citation
D. Curtis, USE OF SIBLINGS AS CONTROLS IN CASE-CONTROL ASSOCIATION STUDIES, Annals of Human Genetics, 61, 1997, pp. 319-333
Citations number
8
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
0003-4800
Volume
61
Year of publication
1997
Part
4
Pages
319 - 333
Database
ISI
SICI code
0003-4800(1997)61:<319:UOSACI>2.0.ZU;2-Y
Abstract
The transmission disequilibrium test (TDT) is a simple means to detect association which should only be positive if the marker allele is lin ked to the disease locus, but it cannot be used if parents of affected subjects are unavailable, as can occur when the disease has a late ag e of onset. Although one can sometimes deduce parental genotypes using the siblings of affected cases, reliance on this procedure can introd uce bias and may also result in discarding many families which could p rovide useful information. Instead, it is shown that the use of unaffe cted siblings as controls is, like the TDT, robust against bias due to population stratification and other sources, and is expected only to produce positive results when a marker is both associated and linked w ith the disease locus. The method can have much less power than a case -control study using unrelated controls, but this can be guarded again st by seeking unaffected siblings which are genotypically distinct fro m cases and by focusing only on alleles which are different within pai rs of cases and controls. This yields a pair-wise test for association which can be used for multiallelic markers in a manner exactly analog ous to the extended TDT (ETDT). The use of siblings as controls is sim ple, robust, practical and worthy of further consideration.