title: Testing association in the presence of linkage using the GRE and multiple markers.
abstract: It has recently been shown that testing for association in the presence of linkage using a score test based on a gamma random effects (GRE) model is substantially more powerful than using the Family-Based Association Test. A reason for the increased power lies in better specification of the within family correlation structure, induced by linkage. The GRE, as presented in (Jonasdottir et al. 2007 Genet Epidemiol. 31:528-540), only considers one marker at a time and does not readily handle missing parental information. Here we extend the GRE to incorporate information from more than one marker. This extension leads to a haplotype GRE test and also to efficient handling of missing data on parental genotypes. We show that the haplotype GRE, the H-GRE, is substantially more powerful than the haplotype FBAT, the Haplotype-Based-Association Test. We demonstrate the usefulness of the extended GRE, by reanalyzing the collaborative study on the genetics of alcoholism data, allowing for missing parental information.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. gudrun.jonasdottir@ki.se
authors.forename: Gudrun
authors.initials: G
authors.lastname: Jonasdottir
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Juni
authors.initials: J
authors.lastname: Palmgren
mesh_terms: D000437:Alcoholism / Q000235:genetics; D005720:Gamma Rays; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D011886:Radon
chemical_list: D005819:Genetic Markers; D011886:Radon