title: Combining information from linkage and association methods.
abstract: 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.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Marchani
authors.forename: Andrea
authors.initials: A
authors.lastname: Callegaro
authors.forename: E Warwick
authors.initials: EW
authors.lastname: Daw
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Wijsman
mesh_terms: D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D010375:Pedigree; D010641:Phenotype
chemical_list: D005819:Genetic Markers