Abstract
Methods to handle missing data have been an area of statistical research for many years. Little has been done within the context of pedigree analysis. In this paper we present two methods for imputing missing data for polygenic models using family data. The imputation schemes take into account familial relationships and use the observed familial information for the imputation. A traditional multiple imputation approach and multiple imputation or data augmentation approach within a Gibbs sampler for the handling of missing data for a polygenic model are presented.We used both the Genetic Analysis Workshop 13 simulated missing phenotype and the complete phenotype data sets as the means to illustrate the two methods. We looked at the phenotypic trait systolic blood pressure and the covariate gender at time point 11 (1970) for Cohort 1 and time point 1 (1971) for Cohort 2. Comparing the results for three replicates of complete and missing data incorporating multiple imputation, we find that multiple imputation via a Gibbs sampler produces more accurate results. Thus, we recommend the Gibbs sampler for imputation purposes because of the ease with which it can be extended to more complicated models, the consistency of the results, and the accountability of the variation due to imputation.
Highlights
Methods to handle missing data have been a statistical area of research for many years [1]
The two imputation methods were run for three replicates of the GAW13 simulated complete and missing data sets for the phenotypic trait of systolic blood pressure and the covariate of gender at time point 11 (1970) for Cohort 1 and time point 1 (1971) for Cohort 2
The Gibbs sampler and the traditional multiple imputation method can be applied to non-ignorable missing data, such as in cases involving censored phenotype data
Summary
Methods to handle missing data have been a statistical area of research for many years [1]. The goals of this paper are: 1) to present two imputation methods for missing phenotype information, and 2) to compare estimates of the additive polygenic effect using variance components or mixed models between the Genetic Analysis Workshop 13 (GAW13) simulated missing phenotype and the complete phenotype data sets for each imputation method [2,3,4]. The methods for imputation described include traditional multiple imputation and multiple imputation (data augmentation) via a Gibbs sampler, with both methods accounting for the familial information in the imputation. In fitting the polygenic model to produce estimates of the overall mean effect, gender effect, additive genetic variance, and the residual error variance, we used the expectation-maximization (EM) algorithm program PolyEM [5] and a Bayesian analysis involving use of a Gibbs sampler
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