1. ¹Department of Mathematical Sciences, Michigan Technological University, Houghton, MI, USA
2. ²Department of Mathematics, Heilongjiang University, Harbin, China

Correspondence: Dr Q Sha, Department of Mathematical Sciences, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA. Tel: +1 906 487 2146; Fax: +1 906 487 3133; E-mail: qsha@mtu.edu

Received 11 April 2007; Revised 13 June 2007; Accepted 14 June 2007; Published online 25 July 2007.

Abstract

Recently, Steen et al proposed a two-stage approach for genome-wide family-based association studies. In the first stage, a screening test is used to select markers, and in the second stage, a family-based association test is performed on a much smaller set of the selected markers. The two-stage method can be much more powerful than the traditional family-based association tests. In this article, we extend the approach so that it can incorporate parental information and can be applied to an arbitrary pedigree structure. We use simulation studies to evaluate the type I error rates and the power of the proposed methods. Our results show that the two-stage approach that incorporates founders' phenotypes has the correct type I error rates, and is much more powerful than the two-stage approach that uses children's phenotypes only. Also, by carefully choosing the number of markers retained in the first stage, the power of a two-stage approach can be much more than that of the corresponding one-stage approach.