Abstract

BackgroundEstimates of variance components for binary responses in presence of extreme case problems tend to be biased due to an under-identified likelihood. The bias persists even when a normal prior is used for the fixed effects.MethodsA simulation study was carried out to investigate methods for the analysis of binary responses with extreme case problems. A linear mixed model that included a fixed effect and random effects of sire and residual on the liability scale was used to generate binary data. Five simulation scenarios were conducted based on varying percentages of extreme case problems, with true values of heritability equal to 0.07 and 0.17. Five replicates of each dataset were generated and analyzed with a generalized prior (g-prior) of varying weight.ResultsPoint estimates of sire variance using a normal prior were severely biased when the percentage of extreme case problems was greater than 30%. Depending on the percentage of extreme case problems, the sire variance was overestimated when a normal prior was used by 36 to 102% and 25 to 105% for a heritability of 0.17 and 0.07, respectively. When a g-prior was used, the bias was reduced and even eliminated, depending on the percentage of extreme case problems and the weight assigned to the g-prior. The lowest Pearson correlations between true and estimated fixed effects were obtained when a normal prior was used. When a 15% g-prior was used instead of a normal prior with a heritability equal to 0.17, Pearson correlations between true and fixed effects increased by 11, 20, 23, 27, and 60% for 5, 10, 20, 30 and 75% of extreme case problems, respectively. Conversely, Pearson correlations between true and estimated fixed effects were similar, within datasets of varying percentages of extreme case problems, when a 5, 10, or 15% g-prior was included. Therefore this indicates that a model with a g-prior provides a more adequate estimation of fixed effects.ConclusionsThe results suggest that when analyzing binary data with extreme case problems, bias in the estimation of variance components could be eliminated, or at least significantly reduced by using a g-prior.

Highlights

  • Estimates of variance components for binary responses in presence of extreme case problems tend to be biased due to an under-identified likelihood

  • The sire variances decreased with an increase in the percentage of g-prior used in the threshold analysis

  • Analysis 15G yielded point estimates extremely similar to the true value for the 5E (0.048) and 10E (0.050) data

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Summary

Introduction

Estimates of variance components for binary responses in presence of extreme case problems tend to be biased due to an under-identified likelihood. It is well known that when the binary responses (1 = cases and 0 = controls) associated with a particular level of an effect fall within the same category, being either all ones or all zeros (known as extreme case problems or ECP), the likelihood is under-identified [1] and variance components tend to be biased. Moreno et al [3] reported a reduction in the bias when a Gaussian probability density function was assigned to the prior distribution of the fixed effects. A simulation using a sire model was used to test the effect of the g-prior in the presence of ECP

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