<p>Hypercholesterolemia is the presence of high levels of cholesterol in the blood, and it is one of the major factors for the development of long-term complications in T1D patients.</p> <p>In the thesis, we studied 1303 Caucasians with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT). With the experience of diabetes study, many factors are associated with diabetes complications, they are age, gender, cohort, treatment, diabetes duration, body mass index (BMI), exercise, insulin dose, etc. We mainly focus on which factors are associated with total cholesterol (CHL) analysis in the thesis.</p> <p>Many measures were collected monthly, quarterly or yearly for average 6.5 years from 1983 to 1993. We used annually lipid measures of DCCT because of their values are sufficient and complete, and they belong to longitudinal data.</p> <p>Different methods are discussed in the study, and linear mixed effect models are the appropriate approach to the study. The details of model selection with CHL model analysis are shown, which includes fixed effect selection, random effects selection, and residual correlation structure selection. Then the SNPs were added on three models individually in GWAS. We found locus (rs7412) is not only genome-wide associated with CHL, but also genome-wide associated with LDL.</p> <p>We will assess whether these SNPs are diabetes-specific in the future, and we will add dietary data in the three models to identify locus are associated with the interaction of diet and SNPs.</p> / Master of Science (MSc)

Os experimentos agronômicos que envolvem somente um fator longitudinal são bastante comuns. No entanto, existem casos em que as observações são tomadas considerando dois ou mais desses fatores, como nos casos em que são feitas medidas de uma variável resposta em profundidades diferentes ao longo do tempo, por exemplo. Admite-se que essas observações, tomadas de modo sistemático em cada unidade experimental, sejam correlacionadas e as variâncias nos diferentes níveis do fator longitudinal sejam heterogêneas. Com o uso de modelos mistos, essa correlação entre medidas repetidas e a heterogeneidade de variâncias podem ser modeladas convenientemente. Para que esses modelos sejam ajustados a um conjunto de dados envolvendo presença de dois fatores longitudinais, existe a necessidade de se adaptarem algumas estruturas de variâncias e covariâncias que são comuns em experimentos com somente um fator longitudinal. O objetivo do presente trabalho é utilizar a classe dos modelos lineares mistos para estudar a massa seca de raiz no solo de uma plantação de cana-de-açúcar. O experimento foi casualizado em blocos e as parcelas receberam quatro doses de nitrogênio. Foram feitas medidas repetidas ao longo de dois fatores longitudinais, sendo um qualitativo ordinal (profundidades) e um quantitativo (distâncias da linha de plantio). Por meio dos testes de razão de verossimilhanças, de Wald e utilizando os critérios de informação AIC e BIC, selecionou-se uma estrutura de covariâncias parcimoniosa e outra estrutura para explicar o comportamento médio das respostas. A verificação do ajuste foi feita por meio de gráficos de diagnósticos de resíduos. / Agronomic experiments involving only one longitudinal factor are quite common. However, there are cases that the observations are made by considering two or more of these factors such as where measurements are made in a response variable at different depths along the time, for example. It is admitted that these observations, taken in a systematic way in each experimental unit are correlated and variances are heterogeneous in different levels of longitudinal factor. Using mixed models, this correlation between repeated measures and heterogeneity of variances can be modeled conveniently. To fit these models to data set involving presence of two longitudinal factors, there is need to adapt some variance and covariance structures that are common in experiments with only one longitudinal factor. The objective of this work is to use the class of linear mixed models to study the dry root mass in the soil of a plantation of cane sugar. The experiment was the randomized complete blocks design and parcels received four doses of nitrogen. Repeated measurements were made along two longitudinal factors being one ordinal qualitative (depths) and one quantitative (distances from the row). With the aid of likelihood ratio, Wald tests and using the AIC and BIC information criteria, we selected a parsimonious covariance structure and another structure to explain the average behavior of the responses. Checking the fit was made using diagnostic graphics of residuals.

The focus in this thesis is on the calculations of an empirical null distributionfor likelihood ratio tests testing either separable or double separable covariancematrix structures versus an unstructured covariance matrix. These calculationshave been performed for various dimensions and sample sizes, and are comparedwith the asymptotic χ2-distribution that is commonly used as an approximative distribution. Tests of separable structures are of particular interest in cases when data iscollected such that more than one relation between the components of the observationis suspected. For instance, if there are both a spatial and a temporalaspect, a hypothesis of two covariance matrices, one for each aspect, is reasonable.

Os experimentos agronômicos que envolvem somente um fator longitudinal são bastante comuns. No entanto, existem casos em que as observações são tomadas considerando dois ou mais desses fatores, como nos casos em que são feitas medidas de uma variável resposta em profundidades diferentes ao longo do tempo, por exemplo. Admite-se que essas observações, tomadas de modo sistemático em cada unidade experimental, sejam correlacionadas e as variâncias nos diferentes níveis do fator longitudinal sejam heterogêneas. Com o uso de modelos mistos, essa correlação entre medidas repetidas e a heterogeneidade de variâncias podem ser modeladas convenientemente. Para que esses modelos sejam ajustados a um conjunto de dados envolvendo presença de dois fatores longitudinais, existe a necessidade de se adaptarem algumas estruturas de variâncias e covariâncias que são comuns em experimentos com somente um fator longitudinal. O objetivo do presente trabalho é utilizar a classe dos modelos lineares mistos para estudar a massa seca de raiz no solo de uma plantação de cana-de-açúcar. O experimento foi casualizado em blocos e as parcelas receberam quatro doses de nitrogênio. Foram feitas medidas repetidas ao longo de dois fatores longitudinais, sendo um qualitativo ordinal (profundidades) e um quantitativo (distâncias da linha de plantio). Por meio dos testes de razão de verossimilhanças, de Wald e utilizando os critérios de informação AIC e BIC, selecionou-se uma estrutura de covariâncias parcimoniosa e outra estrutura para explicar o comportamento médio das respostas. A verificação do ajuste foi feita por meio de gráficos de diagnósticos de resíduos. / Agronomic experiments involving only one longitudinal factor are quite common. However, there are cases that the observations are made by considering two or more of these factors such as where measurements are made in a response variable at different depths along the time, for example. It is admitted that these observations, taken in a systematic way in each experimental unit are correlated and variances are heterogeneous in different levels of longitudinal factor. Using mixed models, this correlation between repeated measures and heterogeneity of variances can be modeled conveniently. To fit these models to data set involving presence of two longitudinal factors, there is need to adapt some variance and covariance structures that are common in experiments with only one longitudinal factor. The objective of this work is to use the class of linear mixed models to study the dry root mass in the soil of a plantation of cane sugar. The experiment was the randomized complete blocks design and parcels received four doses of nitrogen. Repeated measurements were made along two longitudinal factors being one ordinal qualitative (depths) and one quantitative (distances from the row). With the aid of likelihood ratio, Wald tests and using the AIC and BIC information criteria, we selected a parsimonious covariance structure and another structure to explain the average behavior of the responses. Checking the fit was made using diagnostic graphics of residuals.