| Description |
The CEPH (Centre d'Etude du Polymorphisme Humain) project began in 1984 as a collaborative effort to map genetic markers using a set of randomly ascertained families. Since 1997, members of the subset of CEPH families that reside in Utah have been measured for a large number of quantitative traits, which will be tested for linkage by a number of investigators. Therefore, it was very useful to identify statistical characteristics of a trait that influence the power to detect linkage in these families. Using simulations, we concluded that displacement, prevalence, quantitative trait locus variance, and total heritability are significantly related to the power. In addition to the simulation study, we applied statistical techniques to real phenotypic data. The pulmonary function measurements FEV1 (Forced Expiratory Volume in 1 second) and FVC (Forced Vital Capacity) were measured on 264 individuals in 26 Utah CEPH pedigrees. Using segregation analysis, we inferred major gene inheritance for the ratio FEV1/FVC, but could not distinguish between a dominant or recessive mode of inheritance of the inferred locus. Evidence of major gene inheritance was not found for either FEV1 or FVC. Heritability was estimated at 67%, 46%, and 52% for the ratio FEV/FVC, FEV1, and FVC, respectively. Linkage analysis was performed on FEV1, FVC, and the FEV1/FVC ratio using variance components linkage analysis and, for FEV1/FVC, using parametric linkage analysis using parameters from the dominant and recessive models maximized in the segregation analysis of the ratio. Suggestive evidence for parametric linkage was observed on chromosome 2 and chromosome 5 for the ratio FEV1/FVC, with heterogeneity lod scores above 2 in both regions. The variance components method detected linkage to both these regions, which have also been identified in other published studies on other populations. No variance components lod scores above 1.5 were obtained for either FEV1 or FVC. Together, the simulation study and the pulmonary function measurements analysis have demonstrated that the Utah CEPH pedigrees have sufficient information to detect linkage of a marker to a quantitative trait locus depending on the underlying genetic model, and that the analysis of normal variation can lead to gene localization. |
