Abstract
The Framingham Heart Study offspring cohort, a complex data set with irregularly spaced longitudinal phenotype data, was made available as part of Genetic Analysis Workshop 13. To allow an analysis of all of the data simultaneously, a mixed-model- based random-regression (RR) approach was used. The RR accounted for the variation in genetic effects (including marker-specific quantitative trait locus (QTL) effects) across time by fitting polynomials of age. The use of a mixed model allowed both fixed (such as sex) and random (such as familial environment) effects to be accounted for appropriately. Using this method we performed a QTL analysis of all of the available adult phenotype data (26,106 phenotypic records).In addition to RR, conventional univariate variance component techniques were applied. The traits of interest were BMI, HDLC, total cholesterol, and height. The longitudinal method allowed the characterization of the change in QTL effects with aging. A QTL affecting BMI was shown to act mainly at early ages.
Highlights
In this paper we analyze the Framingham Heart Study offspring data using univariate and multivariate variance component techniques, with particular emphasis on how inherited factors related to heart disease change over the life of an individual.at younger ages were not analyzed
We looked at the other four Quantitative Trait Locus (QTL) peaks listed in the univariate results section
The RR model fitted is typically only used for polygenic genetic effects in animal breeding sire models
Summary
In this paper we analyze the Framingham Heart Study offspring data using univariate and multivariate variance component techniques, with particular emphasis on how inherited factors related to heart disease change over the life of an individual. Phenotype data was available for 2885 individuals. 26,106 phenotypic records were used in the full multivariate analysis. Data available There were 4692 individuals in the study. The first had up to 21 trait measures for the 40 years following 1948. The second cohort had up to 5 trait measures for the 20 years following 1971. Genotype data were available for 1702 individuals. The vast majority of individuals in the study had all their measures when they were age 20 or older; measures
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