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Genet Epidemiol. 2000 Feb;18(2):111-27.

Two-stage global search designs for linkage analysis II: including discordant relative pairs in the study.

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  • 1Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.


The optimal two-stage designs proposed by Elston [1992, 1994] for a global search of the genome to locate disease genes by linkage analysis typically halve the cost of a study compared to one-stage designs [Elston et al., 1996]. These designs were based on sampling affected pairs of relatives. Usually, using affected relative pairs is more powerful than using discordant relative pairs [Blackwelder and Elston, 1985; Risch 1990b]. However, in certain situations discordant relative pairs can be as powerful as, or even more powerful than, affected relative pairs. In addition, combining discordant pairs with affected pairs provides a control study. In this paper, we investigate optimal two-stage designs when: 1) using only discordant relative pairs, and 2) combining discordant with affected relative pairs. We show that including discordant relatives pairs into the study not only provides a control, but is also cost effective.

Copyright 2000 Wiley-Liss, Inc.

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