Scholarly Work - Mathematical Sciences
Permanent URI for this collectionhttps://scholarworks.montana.edu/handle/1/8719
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Item Functional Analysis of Variance for Association Studies(Public Library of Science, 2014) Greenwood, Mark C.; Vsevolozhskaya, Olga; Zaykin, Dmitri; Wei, Changshuai; Lu, QingWhile progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain in finding additional unknown genetic variants predisposing to complex diseases. With the advance in next-generation sequencing technologies, sequencing studies have become commonplace in genetic research. The ongoing exome-sequencing and whole-genome-sequencing studies generate a massive amount of sequencing variants and allow researchers to comprehensively investigate their role in human diseases. The discovery of new disease-associated variants can be enhanced by utilizing powerful and computationally efficient statistical methods. In this paper, we propose a functional analysis of variance (FANOVA) method for testing an association of sequence variants in a genomic region with a qualitative trait. The FANOVA has a number of advantages: (1) it tests for a joint effect of gene variants, including both common and rare; (2) it fully utilizes linkage disequilibrium and genetic position information; and (3) allows for either protective or risk-increasing causal variants. Through simulations, we show that FANOVA outperform two popularly used methods – SKAT and a previously proposed method based on functional linear models (FLM), – especially if a sample size of a study is small and/or sequence variants have low to moderate effects. We conduct an empirical study by applying three methods (FANOVA, SKAT and FLM) to sequencing data from Dallas Heart Study. While SKAT and FLM respectively detected ANGPTL 4 and ANGPTL 3 associated with obesity, FANOVA was able to identify both genes associated with obesity.Item Multi-scale clustering of functional data with application to hydraulic gradients in wetlands(Columbia University, New York, 2011) Greenwood, Mark C.; Soida, Richard S.; Sharp, Julia L.; Peck, Rory G.; Rosenberry, Donald O.A new set of methods are developed to perform cluster analysis of functions, motivated by a data set consisting of hydraulic gradients at several locations distributed across a wetland complex. The methods build on previous work on clustering of functions, such as Tarpey and Kinateder (2003) and Hitchcock et al. (2007), but explore functions generated from an additive model decomposition (Wood, 2006) of the original time se- ries. Our decomposition targets two aspects of the series, using an adaptive smoother for the trend and circular spline for the diurnal variation in the series. Different measures for comparing locations are discussed, including a method for efficiently clustering time series that are of different lengths using a functional data approach. The complicated nature of these wetlands are highlighted by the shifting group memberships depending on which scale of variation and year of the study are considered.