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Testing association in the presence of linkage using the GRE and multiple markers
Author(s) -
Jonasdottir Gudrun,
Becker Tim,
Humphreys Keith,
Palmgren Juni
Publication year - 2008
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20315
Subject(s) - linkage (software) , association (psychology) , genetics , biology , computational biology , association mapping , gene , psychology , single nucleotide polymorphism , genotype , psychotherapist
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. Genet. Epidemiol . 2008. © 2008 Wiley‐Liss, Inc.