Estimation of the mean quality-adjusted survival using a multistate model for the sojourn times

In clinical trials, it may be of interest taking into account physical and emotional well-being in addition to survival when comparing treatments. Quality-adjusted survival time has the advantage of incorporating information about both survival time and quality-of-life. In this paper, we discuss the estimation of the expected value of the quality-adjusted survival, based on multistate models for the sojourn times in health states. Semiparametric and parametric (with exponential distribution) approaches are considered. A simulation study is presented to evaluate the performance of the proposed estimator and the jackknife resampling method is used to compute bias and variance of the estimator. (C) 2007 Elsevier B.V. All rights reserved.

Novel Statistical Methods in Quantitative Genetics : Modeling Genetic Variance for Quantitative Trait Loci Mapping and Genomic Evaluation

This thesis develops and evaluates statistical methods for different types of genetic analyses, including quantitative trait loci (QTL) analysis, genome-wide association study (GWAS), and genomic evaluation. The main contribution of the thesis is to provide novel insights in modeling genetic variance, especially via random effects models. In variance component QTL analysis, a full likelihood model accounting for uncertainty in the identity-by-descent (IBD) matrix was developed. It was found to be able to correctly adjust the bias in genetic variance component estimation and gain power in QTL mapping in terms of precision.  Double hierarchical generalized linear models, and a non-iterative simplified version, were implemented and applied to fit data of an entire genome. These whole genome models were shown to have good performance in both QTL mapping and genomic prediction. A re-analysis of a publicly available GWAS data set identified significant loci in Arabidopsis that control phenotypic variance instead of mean, which validated the idea of variance-controlling genes.  The works in the thesis are accompanied by R packages available online, including a general statistical tool for fitting random effects models (hglm), an efficient generalized ridge regression for high-dimensional data (bigRR), a double-layer mixed model for genomic data analysis (iQTL), a stochastic IBD matrix calculator (MCIBD), a computational interface for QTL mapping (qtl.outbred), and a GWAS analysis tool for mapping variance-controlling loci (vGWAS).

Estimation of Parameters in Random Effect Models with Incidence Matrix Uncertainty

Random effect models have been widely applied in many fields of research. However, models with uncertain design matrices for random effects have been little investigated before. In some applications with such problems, an expectation method has been used for simplicity. This method does not include the extra information of uncertainty in the design matrix is not included. The closed solution for this problem is generally difficult to attain. We therefore propose an two-step algorithm for estimating the parameters, especially the variance components in the model. The implementation is based on Monte Carlo approximation and a Newton-Raphson-based EM algorithm. As an example, a simulated genetics dataset was analyzed. The results showed that the proportion of the total variance explained by the random effects was accurately estimated, which was highly underestimated by the expectation method. By introducing heuristic search and optimization methods, the algorithm can possibly be developed to infer the 'model-based' best design matrix and the corresponding best estimates.

Estimation of DSGE Models: A Monte Carlo Analysis

Neste trabalho investigamos as propriedades em pequena amostra e a robustez das estimativas dos parâmetros de modelos DSGE. Tomamos o modelo de Smets and Wouters (2007) como base e avaliamos a performance de dois procedimentos de estimação: Método dos Momentos Simulados (MMS) e Máxima Verossimilhança (MV). Examinamos a distribuição empírica das estimativas dos parâmetros e sua implicação para as análises de impulso-resposta e decomposição de variância nos casos de especificação correta e má especificação. Nossos resultados apontam para um desempenho ruim de MMS e alguns padrões de viés nas análises de impulso-resposta e decomposição de variância com estimativas de MV nos casos de má especificação considerados.

Estimation of genetic parameters for partial egg production periods by means of random regression models

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Heritability estimation in early generations of two-way crosses in soybean

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estimation of genetic parameters for body weights, scrotal circumference, and testicular volume measured at different ages in Nellore cattle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Bayesian inference in genetic parameter estimation of visual scores in Nellore beef-cattle

The aim of this study was to estimate the components of variance and genetic parameters for the visual scores which constitute the Morphological Evaluation System (MES), such as body structure (S), precocity (P) and musculature (M) in Nellore beef-cattle at the weaning and yearling stages, by using threshold Bayesian models. The information used for this was gleaned from visual scores of 5,407 animals evaluated at the weaning and 2,649 at the yearling stages. The genetic parameters for visual score traits were estimated through two-trait analysis, using the threshold animal model, with Bayesian statistics methodology and MTGSAM (Multiple Trait Gibbs Sampler for Animal Models) threshold software. Heritability estimates for S, P and M were 0.68, 0.65 and 0.62 (at weaning) and 0.44, 0.38 and 0.32 (at the yearling stage), respectively. Heritability estimates for S, P and M were found to be high, and so it is expected that these traits should respond favorably to direct selection. The visual scores evaluated at the weaning and yearling stages might be used in the composition of new selection indexes, as they presented sufficient genetic variability to promote genetic progress in such morphological traits.

Influence of data structure on the estimation of the additive genetic direct and maternal covariance for early growth traits in Nellore cattle

The objective of the present study was to investigate the effect of data structure on estimated genetic parameters and predicted breeding values of direct and maternal genetic effects for weaning weight (WW) and weight gain from birth to weaning (BWG), including or not the genetic covariance between direct and maternal effects. Records of 97,490 Nellore animals born between 1993 and 2006, from the Jacarezinho cattle raising farm, were used. Two different data sets were analyzed: DI_all, which included all available progenies of dams without their own performance; DII_all, which included DI_all + 20% of recorded progenies with maternal phenotypes. Two subsets were obtained from each data set (DI_all and DII_all): DI_1 and DII_1, which included only dams with three or fewer progenies; DI_5 and DII_5, which included only dams with five or more progenies. (Co)variance components and heritabilities were estimated by Bayesian inference through Gibbs sampling using univariate animal models. In general, for the population and traits studied, the proportion of dams with known phenotypic information and the number of progenies per dam influenced direct and maternal heritabilities, as well as the contribution of maternal permanent environmental variance to phenotypic variance. Only small differences were observed in the genetic and environmental parameters when the genetic covariance between direct and maternal effects was set to zero in the data sets studied. Thus, the inclusion or not of the genetic covariance between direct and maternal effects had little effect on the ranking of animals according to their breeding values for WW and BWG. Accurate estimation of genetic correlations between direct and maternal genetic effects depends on the data structure. Thus, this covariance should be set to zero in Nellore data sets in which the proportion of dams with phenotypic information is low, the number of progenies per dam is small, and pedigree relationships are poorly known. (c) 2012 Elsevier B.V. All rights reserved.

Estimation of genetic parameters for milk yield in Murrah buffaloes by Bayesian inference

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estimation of variances of the effects of incomplete diallels using a matrix approach

A matrix approach is described for assessing the variance of effects in incomplete diallels designs. The method is illustrated by reference to simulated complete and incomplete diallels using different combinations of constraints, average degree of dominance and, for the incomplete diallel, number of hybrids. Our results showed that caution should be taken in working with incomplete diallels under conditions of overdominance because there were changes in the rank of the genotypes when the excluded hybrid had parents with a low frequency of the favorable allele (i.e. the allele which increases expression of a character). The expression described in this paper is a rapid and safe approach to estimate variances and covariances of the effects of contrasts of incomplete diallels. Copyright by the Brazilian Society of Genetics.

Genetic effects on preweaning weight gain of Nelore-Hereford calves according to different models and estimation methods

Additive and nonadditive genetic effects on preweaning weight gain (PWG) of a commercial crossbred population were estimated using different genetic models and estimation methods. The data set consisted of 103,445 records on purebred and crossbred Nelore-Hereford calves raised under pasture conditions on farms located in south, southeast, and middle west Brazilian regions. In addition to breed additive and dominance effects, the models including different epistasis covariables were tested. Models considering joint additive and environment (latitude) by genetic effects interactions were also applied. In a first step, analyses were carried out under animal models. In a second step, preadjusted records were analyzed using ordinary least squares (OLS) and ridge regression (RR). The results reinforced evidence that breed additive and dominance effects are not sufficient to explain the observed variability in preweaning traits of Bos taurus x Bos indicus calves, and that genotype x environment interaction plays an important role in the evaluation of crossbred calves. Data were ill-conditioned to estimate the effects of genotype x environment interactions. Models including these effects presented multicolinearity problems. In this case, RR seemed to be a powerful tool for obtaining more plausible and stable estimates. Estimated prediction error variances and variance inflation factors were drastically reduced, and many effects that were not significant under ordinary least squares became significant under RR. Predictions of PWG based on RR estimates were more acceptable from a biological perspective. In temperate and subtropical regions, calves with intermediate genetic compositions (close to 1/2 Nelore) exhibited greater predicted PWG. In the tropics, predicted PWG increased linearly as genotype got closer to Nelore. ©2006 American Society of Animal Science. All rights reserved.

Estimation of spontaneous blinking main sequence in normal subjects and patients with Graves' upper eyelid retraction

Purpose. We quantified the main sequence of spontaneous blinks in normal subjects and Graves' disease patients with upper eyelid retraction using a nonlinear and two linear models, and examined the variability of the main sequence estimated with standard linear regression for 10-minute periods of time. Methods. A total of 20 normal subjects and 12 patients had their spontaneous blinking measured with the magnetic search coil technique when watching a video during one hour. The main sequence was estimated with a power-law function, and with standard and trough the origin linear regressions. Repeated measurements ANOVA was used to test the mean sequence stability of 10-minute bins measured with standard linear regression. Results. In 95% of the sample the correlation coefficients of the main sequence ranged from 0.60 to 0.94. Homoscedasticity of the peak velocity was not verified in 20% of the subjects and 25% of the patients. The power-law function provided the best main sequence fitting for subjects and patients. The mean sequence of 10-minute bins measured with standard linear regression did not differ from the one-hour period value. For the entire period of observation and the slope obtained by standard linear regression, the main sequence of the patients was reduced significantly compared to the normal subjects. Conclusions. Standard linear regression is a valid and stable approximation for estimating the main sequence of spontaneous blinking. However, the basic assumptions of the linear regression model should be examined on an individual basis. The maximum velocity of large blinks is slower in Graves' disease patients than in normal subjects. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Multiple-trait random regression models for the estimation of genetic parameters for milk, fat, and protein yield in buffaloes

In this study, genetic parameters for test-day milk, fat, and protein yield were estimated for the first lactation. The data analyzed consisted of 1,433 first lactations of Murrah buffaloes, daughters of 113 sires from 12 herds in the state of São Paulo, Brazil, with calvings from 1985 to 2007. Ten-month classes of lactation days were considered for the test-day yields. The (co)variance components for the 3 traits were estimated using the regression analyses by Bayesian inference applying an animal model by Gibbs sampling. The contemporary groups were defined as herd-year-month of the test day. In the model, the random effects were additive genetic, permanent environment, and residual. The fixed effects were contemporary group and number of milkings (1 or 2), the linear and quadratic effects of the covariable age of the buffalo at calving, as well as the mean lactation curve of the population, which was modeled by orthogonal Legendre polynomials of fourth order. The random effects for the traits studied were modeled by Legendre polynomials of third and fourth order for additive genetic and permanent environment, respectively, the residual variances were modeled considering 4 residual classes. The heritability estimates for the traits were moderate (from 0.21-0.38), with higher estimates in the intermediate lactation phase. The genetic correlation estimates within and among the traits varied from 0.05 to 0.99. The results indicate that the selection for any trait test day will result in an indirect genetic gain for milk, fat, and protein yield in all periods of the lactation curve. The accuracy associated with estimated breeding values obtained using multi-trait random regression was slightly higher (around 8%) compared with single-trait random regression. This difference may be because to the greater amount of information available per animal. © 2013 American Dairy Science Association.

Genetic parameter estimation for pre- and post-weaning traits in Brahman cattle in Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)