This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Haseman and Elston (H-E) proposed a robust test to detect linkage between a quantitative trait and a genetic marker. In their method the squared sib-pair trait difference is regressed on the estimated proportion of alleles at a locus shared identical by descent by sib pairs. Our latest extension of this method makes it applicable to longitudinal data. The proposed model is a mixed model having several random effects. As response variable, we investigated the sibship sample mean corrected cross-product and the BLUP-mean corrected cross product, comparing them with the original squared difference, the overall mean corrected cross-product, and the weighted average of the squared difference and the squared mean-corrected sum. The proposed model allows for the correlation structure of longitudinal data. Also, the model can test for gene x time interaction to discover genetic variation over time. The model was applied in an analysis of the Genetic Analysis Workshop 13 (GAW 13) simulated dataset for a quantitative trait simulating systolic blood pressure. Independence models did not preserve the test sizes, while the mixed models with both family and sibpair random effects tended to preserve size well.
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