title: Two-stage global search designs for linkage analysis II: including discordant relative pairs in the study.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.forename: R C
authors.initials: RC
authors.lastname: Elston
mesh_terms: D030342:Genetic Diseases, Inborn / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D015233:Models, Statistical