Guo X, Elston R C
Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.
Genet Epidemiol. 2000 Feb;18(2):111-27. doi: 10.1002/(SICI)1098-2272(200002)18:2<111::AID-GEPI2>3.0.CO;2-M.
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.
埃尔斯顿[1992年、1994年]提出的用于通过连锁分析在全基因组范围内寻找疾病基因的最优两阶段设计，与一阶段设计相比[埃尔斯顿等人，1996年]，通常能将研究成本减半。这些设计基于对患病亲属对进行抽样。通常，使用患病亲属对比使用不一致亲属对更具效力[布莱克韦尔德和埃尔斯顿，1985年；里施，1990年b]。然而，在某些情况下，不一致亲属对可能与患病亲属对效力相当，甚至更具效力。此外，将不一致对与患病对相结合可提供一项对照研究。在本文中，我们研究了以下两种情况下的最优两阶段设计：1）仅使用不一致亲属对，以及2）将不一致亲属对与患病亲属对相结合。我们表明，将不一致亲属对纳入研究不仅能提供对照，而且具有成本效益。
