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Indiana University-Purdue University Indianapolis (IUPUI) / Recent genome-wide association studies (GWAS) have identified many common genetic variants that are associated with women’s reproductive timing characteristics including ages at menarche and at natural menopause. However, the associations of these variants with other human health related phenotypes such as blood pressure, cancer, diabetes, obesity, and body height growth have not been well studied. No published studies to our knowledge have directly assessed the genetic influence of reproductive timing related variants on the aforementioned common traits. A better understanding of pleiotropic effects of these variants is important because it will help elucidate the precise mechanisms of common traits/diseases such as hypertension which have not been fully understood so far, and give clues for developing better solutions for disease prevention and treatment. We, therefore, conducted three studies to explore genetic variant effects on blood pressure and body height growth. In the first study, we analyzed data from a local cohort of 601 healthy adolescents from Indianapolis schools. Mixed effect model analysis revealed that 11 reproductive related single nucleotide polymorphisms (SNPs) were significantly associated with blood pressure in the study subjects. In order to assess if these genetic effects extended to the adult blood pressure, we performed the second study to investigate the genetic effect on blood pressure in adults. We used the summary statistics obtained from the two large international GWAS consortia, the Blood Pressure Consortium and the ReproGen Consortium. Bivariate analyses showed that more than 100 SNPs were associated with both blood pressure and reproductive timing. As the blood pressure development is closely related to somatic growth, we conducted the third study to exam the genetic effect of reproductive-timing related variants on the linear growth from the aforementioned local cohort. We identified 8 genetic variants significantly associated with the catch-up of linear growth in the study subjects. In conclusion, these three studies collectively provided evidence in support of the pleiotropic effects of the reproductive timing variants, suggesting the common genetic basis underlying the correlated traits. Future research is needed to validate the findings. / 2 years

Thesis--Copenhagen. / Summary in Danish. Bibliography: p. [129]-131.

Thesis--Copenhagen. / Summary in Danish. Bibliography: p. [129]-131.

Thesis--Copenhagen. / Summary in Danish. Bibliography: p. [129]-131.

During the past few years a development of breeding llamas and alpacas took place in Czech Republic. Increasing interest in those animals entails the need to determine how they respond to the conditions of our country. The aim of this thesis is to evaluate the growth ability of crias, some of the physical dimensions (withers height) and bodyweight of adult llamas. The same indicators are to be evaluated for alpacas as well. The results are to be compared with the standard for llamas and alpacas. A total of 104 animals were measured and weighted, namely 44 llamas and 60 alpacas, and 280 pairs of weight and height data were obtained. Weighing and measuring of adult llamas and alpacas took place once a year around the end of August for two years (2009 and 2010). Young llamas were weighed and measured at approximately monthly intervals according to the possibilities of their breeders. Young alpacas were weighed at approximately weekly intervals. The thesis is divided into two parts. The first part evaluates llamas. It was discovered that the average birth weight of llamas in the Czech Republic is 11 kg. Once mature, they reach an average live weight of 130.3 kg and average height of 110.2 cm. Average daily gains were observed as follows: from birth to 7 weeks 0.20 kg per day, from 7 weeks to 24 weeks 0.18 kg per day and from 24 to 72 weeks 0.13 kg per day. The second part of this thesis is devoted to alpacas, for which the same parameters as for the llamas were monitored. It was found that the average birth weight of alpacas in the Czech Republic is 6.5 kg. Once mature, they reach an average live weight of 65.6 kg and average height at 88.4 cm. Average daily gains are at the following levels: from birth to 7 weeks 0.1 kg per day, from 7 weeks to 24 weeks 0.09 kg per day and from 24 weeks to 72 weeks 0.08 kg per day. It was found that these two species reach final physical maturity later in the Czech Republic than stated by literature. Compared to the standard, most of the llamas and alpacas are up to their standards.

This dissertation has multiple aims in studying hierarchical linear models in biomedical data analysis. In Chapter 1, the novel idea of studying the durations of adolescent growth spurts as a predictor of adulthood obesity is defined, established, and illustrated. The concept of contextual effects modeling is introduced in this first section as we study secular trend of adulthood obesity and how this trend is mitigated by the durations of individual adolescent growth spurts and the secular average length of adolescent growth spurts. It is found that individuals with longer periods of fast height growth in adolescence are more prone to having favorable BMI profiles in adulthood. In Chapter 2 we study the estimation of contextual effects in a hierarchical generalized linear model (HGLM). We simulate data and study the effects using the higher level group sample mean as the estimate for the true mean versus using an Empirical Bayes (EB) approach (Shin and Raudenbush 2010). We study this comparison for logistic, probit, log-linear, ordinal and nominal regression models. We find that in general the EB estimate lends a parameter estimate much closer to the true value, except for cases with very small variability in the upper level, where it is a more complicated situation and there is likely no need for contextual effects analysis. In Chapter 3 the HGLM studies are made clearer with large-scale simulations. These large scale simulations are shown for logistic regression and probit regression models for binary outcome data. With repetition we are able to establish coverage percentages of the confidence intervals of the true contextual effect. Coverage percentages show the percentage of simulations that have confidence intervals containing the true parameter values. Results confirm observations from the preliminary simulations in the previous section of this paper, and an accompanying example of adulthood hypertension shows how these results can be used in an application.

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Hurricane Katrina had a devastating impact on bottomland hardwood forests in 2005 resulting in damage to nearly 1.2 billion cubic meters of timber. Following such a natural disaster, natural regeneration is typically not a viable option because the seed source has been destroyed on site. Therefore, an economically efficient method of artificial regeneration is considered the most appropriate technique for reforesting these damaged areas. However, few studies have evaluated comparative research that examined early survival and growth performance of various oak species and stock types in such planting settings. This project was implemented in an effort to expand upon what is already known from previous artificial regeneration attempts on Hurricane Katrina damaged lands. Bareroot, conventional containerized, and large potted EKOgrownTM seedlings of cherrybark oak (Quercus pagoda Raf.) and willow oak (Quercus phellos L.) were planted on two sites located in south Mississippi. Survival was assessed monthly and at the end of each growing season, whereas height and groundline diameter (GLD) were measured immediately post planting and at the end of each growing season. Analysis of variance (ANOVA) and Tukey-Kramer multiple comparisons procedure (MCP), where appropriate, were performed to determine any significant differences. After the first growing season, cherrybark oak did not exhibit a substantial difference regarding survival performance when compared to willow oak (75.5 percent and 76.5 percent, respectively). After two growing seasons, willow oak exhibited considerably greater survival (74.0 percent) overall when compared to cherrybark oak (70.5 percent). Bareroot seedlings had the highest survival (87.2 percent). Conventional containerized seedlings had unacceptable survival (47.5 percent) and EKOgrownTM seedlings had acceptable survival (82.0 percent). EKOgrownTM seedlings demonstrated the best overall GLD growth of all planting stocks (3.9 mm respectively). Bareroot seedlings had the second best overall GLD growth (1.5 mm) and conventional containerized had the least amount of overall GLD growth (0.8 mm). Overall height growth when comparing all three planting stocks bareroot, conventional containerized, and EKOgrownTM were similar to one another (-3.5cm, -0.8cm, and -3.6cm respectively). Therefore, based on an overall consideration of cost and performance, bareroot seedlings are considered the most effective option of the two species considered for artificial regeneration utilized in this study.

Pacific silver fir (Abies amabilis (Dougl. ex Loud.) Forbes) is an important timber crop species in coastal forests of B.C. Its range extends from sea-level to almost timberline, and from the hypermaritime region on the west coast of Vancouver Island to the subcontinental region on the leeward side of the Coast Mountains. With this relatively wide climatic amplitude, a large variability in the height growth pattern of Pacific silver fir can be expected, since climate is considered to be the most influential determinant of the trajectory of height over age of forest trees. This variability, however, is not reflected in the height growth curves and site index tables used to estimate Pacific silver fir site index, since the curves and tables were developed from low-elevation stands on Vancouver Island. Consequently, when these curves and tables are applied to high-elevation or submaritime stands, we get biased estimates of site index. Accurate estimates of site index are necessary for accurate yield predictions. Furthermore, they are essential for making rational decisions about whether to cut the forest in situations where potential tree growth is marginal, such as in high-elevation forests.