The power to detect genetic linkage for quantitative traits in the Utah CEPH pedigrees.

Quantitative trait phenotypes and linked marker genotypes were simulated for a range of models with different sets of assumptions based on displacement, prevalence, and heritability of the trait in 30 Utah Centre d'Etude du Polymorphisme Humain (CEPH) families. The gain in power by the addition of 15 families was also estimated by extrapolation. Power was evaluated using both parametric single locus (PSL) models and variance components (VC) methods for two situations: (1) a single marker with 75% heterozygosity and a recombination fraction of 0.05, and (2) a fully informative marker as an approximation to multipoint analysis. When the simulation and analysis models were both dominant with the same prevalence, power > or =80% for lod >3 was estimated when quantitative trait locus variance was > or =40% with a displacement of 2.5 or 3. Power was 5-15% lower for recessive models compared to dominant models. With the addition of 15 families, an average increase in power of 17% and 22% was estimated for the dominant and recessive models, respectively. In PSL analyses, power was estimated at < or =20% when the dominance was misspecified. This investigation delineates parameter conditions under which this unique sample affords adequate power to detect linkage using both PSL and VC methods.

Genetic analysis of a complex trait in the Utah Genetic Reference Project: a major locus for PTC taste ability on chromosome 7q and a secondary locus on chromosome 16p.

The ability to taste phenylthiocarbamide (PTC) shows complex inheritance in humans. We obtained a quantitative measure of PTC tasting ability in 267 members of 26 large three-generation families that were part of a set of CEPH families that had been used for genetic mapping. Significant bimodality was found for the distribution of age and gender adjusted scores (P<0.001), with estimated means of 3.16 (SD=1.80) and 9.26 (SD=1.54). Using the extensive genotyping available in these families from the genetic mapping efforts, we performed a genome scan by using 1324 markers with an average spacing of 4 cM. Analyses were first carried out with a recessive genetic model that has traditionally been assumed for the trait, and a threshold score of 8.0 delineating tasters from non-tasters. In this qualitative analysis, the maximum genome-wide lod score was 4.74 at 246 cM on chromosome 7; 17 families showed segregation of the dichotomous PTC phenotype. No other lod scores were significant; the next highest score was on chromosome 10 (lod=1.64 at 85 cM), followed by chromosome 3 (lod=1.29 at 267 cM). Because PTC taste ability exhibited substantial quantitative variation, the quantitative trait was also analyzed by using a variance components approach in SOLAR. The maximum quantitative genome-wide lod score was 8.85 at 246 cM on chromosome 7. Evidence for other possible quantitative loci was found on chromosomes 1 (lod=2.31 at 344 cM) and 16 (lod=2.01 at 14 cM). A subsequent two-locus whole-genome scan conditional on the chromosome 7 quantitative trait locus identified the chromosome 16 locus (two-locus lod=3.33 at 14 cM).