Genetic analysis of phenotypes derived from longitudinal data: Presentation Group 1 of Genetic Analysis Workshop 13

The participants of Presentation Group 1 used the GAW13 data to derive new phenotypes, which were then analyzed for linkage and, in one case, for association to the genetic markers. Since the trait measurements ranged over longer time periods, the participants looked at the time dependence of particular traits in addition to the trait itself. The phenotypes analyzed with the Framingham data can be roughly divided into 1) body weight-related traits, which also include a type 2 diabetes progression trait, and 2) traits related to systolic blood pressure. Both trait classes are associated with metabolic syndrome. For traits related to body weight, linkage was consistently identified by at least two participating groups to genetic regions on chromosomes 4, 8, 11, and 18. For systolic blood pressure, or its derivatives, at least two groups obtained linkage for regions on chromosomes 4, 6, 8, 11, 14, 16, and 19. Five of the 13 participating groups focused on the simulated data. Due to the rather sparse grid of microsatellite markers, an association analysis for several traits was not successful. Linkage analysis of hypertension and body mass index using LODs and heterogeneity LODs (HLODs) had low power. For the glucose phenotype, a combination of random coefficient regression models and variance component linkage analysis turned out to be strikingly powerful in the identification of a trait locus simulated on chromosome 5. Haseman-Elston regression methods, applied to the same phenotype, had low power, but the above-mentioned chromosome 5 locus was not included in this analysis.