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Combining information from linkage and association methods
Author(s) -
Marchani Elizabeth E.,
Callegaro Andrea,
Daw E. Warwick,
Wijsman Ellen M.
Publication year - 2009
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.20477
Subject(s) - linkage (software) , replication (statistics) , identity by descent , computer science , covariate , genetic association , trait , identification (biology) , data mining , statistics , machine learning , mathematics , biology , genetics , allele , gene , botany , single nucleotide polymorphism , genotype , haplotype , programming language
Group 12 evaluated approaches to incorporate outside information or otherwise optimize traditional linkage and association analyses. The abundance of available data allowed exploration of identity‐by‐descent (IBD) estimation, score statistics, formal combination of linkage and association testing, significance estimation, and replication. We observed that IBD estimation can be optimized with a subset of marker data while estimation of inheritance vectors can provide both IBD estimates and a measure of their uncertainty. Score statistics incorporating covariates or combining association and linkage information performed at least as well as standard approaches while requiring less computation time. The formal combination of linkage and association methods may be fruitful, although the nature of the simulated data limited our conclusions. Estimation of significance may be improved through simulation, correction for cryptic relatedness, and the inclusion of prior information. Replication using real data provided consistent results, though the same was not true of simulated data replicates. Overall, we found that increasing the amount of available data limits analyses due to computational constraints and motivates the need to improve methods for the identification of complex‐trait genes. Genet. Epidemiol . 33 (Suppl. 1):S81–S87, 2009. © 2009 Wiley‐Liss, Inc.