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Potential bias in generalized estimating equations linkage methods under incomplete information
Author(s) -
Lebrec J.,
Putter H.,
van Houwelingen J.C.
Publication year - 2006
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.20097
Subject(s) - gee , generalized estimating equation , linkage (software) , identity by descent , statistics , confidence interval , mathematics , complete information , locus (genetics) , econometrics , biology , genetics , gene , mathematical economics , genotype , haplotype
The mean identity‐by‐descent (IBD) specification used in the Generalized Estimating Equations (GEE) methodology for linkage is only valid, strictly speaking, under the assumption of fully polymorphic markers. In practice, markers often provide only partial IBD information, which can potentially result in inconsistency of the locus location and gene effect estimates obtained by the GEE method. Using both simulations and theory, we identify some realistic conditions about marker information under which the validity of the GEE linkage methods may be arguable. Namely, researchers should not trust the GEE parameters' estimates and their associated confidence intervals in areas of the genome where IBD information is sparse or when this information changes abruptly. We show that properly standardized statistics based on IBD sharing provide a valid alternative. Genet. Epidemiol . 2006. © 2005 Wiley‐Liss Inc.