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Analysis Strategies (analysis + strategy)
Selected AbstractsGenetic association with rheumatoid arthritis,Genetic Analysis Workshop 15: summary of contributions from Group 2GENETIC EPIDEMIOLOGY, Issue S1 2007Marsha A. Wilcox Abstract The papers in presentation group 2 of Genetic Analysis Workshop 15 (GAW15) conducted association analyses of rheumatoid arthritis data. The analyses were carried out primarily in the data provided by the North American Rheumatoid Arthritis Consortium (NARAC). One group conducted analyses in the data provided by the Canadian Rheumatoid Arthritis Genetics Study (CRAGS). Analysis strategies included genome-wide scans, the examination of candidate genes, and investigations of a region of interest on chromosome 18q21. Most authors employed relatively new methods, proposed extensions of existing methods, or introduced completely novel methods for aspects of association analysis. There were several common observations; a group of papers using a variety of methods found stronger association, on chromosomes 6 and 18 and in candidate gene PTPN22 among women with early onset. Generally, models that considered haplotypes or multiple markers showed stronger evidence for association than did single marker analyses. Genet. Epidemiol. 31 (Suppl. 1):S12,S21, 2007. © 2007 Wiley-Liss, Inc. [source] Gene expression analysis in absence epilepsy using a monozygotic twin designEPILEPSIA, Issue 9 2008Ingo Helbig Summary Purpose: To identify genes involved in idiopathic absence epilepsies by analyzing gene expression using a monozygotic (MZ) twin design. Methods: Genome-wide gene expression in lymphoblastoid cell lines (LCLs) was determined using microarrays derived from five discordant and four concordant MZ twin pairs with idiopathic absence epilepsies and five unaffected MZ twin pairs. Gene expression was analyzed using three strategies: discordant MZ twins were compared as matched pairs, MZ twins concordant for epilepsy were compared to control MZ twins, and a singleton design of affected versus unaffected MZ twin individuals was used irrespective of twin pairing. An overlapping gene list was generated from these analyses. Dysregulation of genes recognized from the microarray experiment was validated using quantitative real time PCR (qRT-PCR) in the twin sample and in an independent sample of 18 sporadic absence cases and 24 healthy controls. Results: Sixty-five probe sets were identified from the three combined microarray analysis strategies. Sixteen genes were chosen for validation and nine of these genes confirmed by qRT-PCR in the twin sample. Differential expression for EGR1 (an immediate early gene) and RCN2 (coding for the calcium-binding protein Reticulocalbin 2) were reconfirmed by qRT-PCR in the independent sample. Discussion: Using a unique sample of discordant MZ twins, our study identified genes with altered expression, which suggests novel mechanisms in idiopathic absence epilepsy. Dysregulation of EGR1 and RCN2 is implicated in idiopathic absence epilepsy. [source] Multistage analysis strategies for genome-wide association studies: summary of group 3 contributions to Genetic Analysis Workshop 16GENETIC EPIDEMIOLOGY, Issue S1 2009Rosalind J. Neuman Abstract This contribution summarizes the work done by six independent teams of investigators to identify the genetic and non-genetic variants that work together or independently to predispose to disease. The theme addressed in these studies is multistage strategies in the context of genome-wide association studies (GWAS). The work performed comes from Group 3 of the Genetic Analysis Workshop 16 held in St. Louis, Missouri in September 2008. These six studies represent a diversity of multistage methods of which five are applied to the North American Rheumatoid Arthritis Consortium rheumatoid arthritis case-control data, and one method is applied to the low-density lipoprotein phenotype in the Framingham Heart Study simulated data. In the first stage of analyses, the majority of studies used a variety of screening techniques to reduce the noise of single-nucleotide polymorphisms purportedly not involved in the phenotype of interest. Three studies analyzed the data using penalized regression models, either LASSO or the elastic net. The main result was a reconfirmation of the involvement of variants in the HLA region on chromosome 6 with rheumatoid arthritis. The hope is that the intense computational methods highlighted in this group of papers will become useful tools in future GWAS. Genet. Epidemiol. 33 (Suppl. 1):S19,S23, 2009. © 2009 Wiley-Liss, Inc. [source] Practical pharmacovigilance analysis strategiesPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2003A. Lawrence Gould Abstract Purpose To compare two recently proposed Bayesian methods for quantitative pharmacovigilance with respect to assumptions and results, and to describe some practical strategies for their use. Methods The two methods were expressed in common terms to simplify identifying similarities and differences, some extensions to both methods were provided, and the empirical Bayes method was applied to accumulated experience on a new antihypertensive drug to elucidate the pattern of adverse-event reporting. Both methods use the logarithm of the proportional risk ratio as the basic metric for association. Results The two methods provide similar numerical results for frequently reported events, but not necessarily when few events are reported. Using a lower 5% quantile of the posterior distribution gives some assurance that potential signals are unlikely to be noise. The calculations indicated that most potential adverse event,drug associations that were well-recognized after 6 years of use could be identified within the first year, that most of the associations identified in the first year persisted over time. Other insights into the pattern of event reporting were also noted. Conclusion Both methods can provide useful early signals of potential drug,event associations that subsequently can be the focus of detailed evaluation by skilled clinicians and epidemiologists. Copyright © 2002 John Wiley & Sons, Ltd. [source] Finding genes underlying human diseaseCLINICAL GENETICS, Issue 2 2009CM Stein With the surge in genome-wide association studies (GWAS), many have asked the question ,Are linkage studies dead?' In this article, we survey the approaches used in mapping human disease genes, reviewing the analysis strategies that preceded and laid the groundwork for GWAS. We note that earlier approaches are still useful and the development of new methodology is warranted. [source] A systems biology approach to understanding atherosclerosisEMBO MOLECULAR MEDICINE, Issue 3 2010Stephen A. Ramsey Abstract Atherosclerosis, a chronic inflammatory disease of the vascular system, presents significant challenges to developing effective molecular diagnostics and novel therapies. A systems biology approach integrating data from large-scale measurements (e.g. transcriptomics, proteomics and genomics) is successfully contributing to deciphering regulatory networks underlying the response of many different cellular systems to perturbations. Such a network analysis strategy using pathway information and data from multiple measurement platforms, tissues and species is a promising approach to elucidate the mechanistic underpinnings of complex diseases. Here, we present our views on the contributions that a systems approach can bring to the study of atherosclerosis, propose ways to tackle the complexity of the disease in a systems manner and review recent systems-level studies of the disease. [source] ,The National Stream Quality Accounting Network: a flux-based approach to monitoring the water quality of large riversHYDROLOGICAL PROCESSES, Issue 7 2001Richard P. Hooper Abstract Estimating the annual mass flux at a network of fixed stations is one approach to characterizing water quality of large rivers. The interpretive context provided by annual flux includes identifying source and sink areas for constituents and estimating the loadings to receiving waters, such as reservoirs or the ocean. Since 1995, the US Geological Survey's National Stream Quality Accounting Network (NASQAN) has employed this approach at a network of 39 stations in four of the largest river basins of the USA: the Mississippi, the Columbia, the Colorado and the Rio Grande. In this paper, the design of NASQAN is described and its effectiveness at characterizing the water quality of these rivers is evaluated using data from the first 3 years of operation. A broad range of constituents was measured by NASQAN, including trace organic and inorganic chemicals, major ions, sediment and nutrients. Where possible, a regression model relating concentration to discharge and season was used to interpolate between chemical observations for flux estimation. For water-quality network design, the most important finding from NASQAN was the importance of having a specific objective (that is, estimating annual mass flux) and, from that, an explicitly stated data analysis strategy, namely the use of regression models to interpolate between observations. The use of such models aided in the design of sampling strategy and provided a context for data review. The regression models essentially form null hypotheses for concentration variation that can be evaluated by the observed data. The feedback between network operation and data collection established by the hypothesis tests places the water-quality network on a firm scientific footing. Published in 2001 by John Wiley & Sons, Ltd. [source] Reliability-based design optimization with equality constraintsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 11 2007Xiaoping Du Abstract Equality constraints have been well studied and widely used in deterministic optimization, but they have rarely been addressed in reliability-based design optimization (RBDO). The inclusion of an equality constraint in RBDO results in dependency among random variables. Theoretically, one random variable can be substituted in terms of remaining random variables given an equality constraint; and the equality constraint can then be eliminated. However, in practice, eliminating an equality constraint may be difficult or impossible because of complexities such as coupling, recursion, high dimensionality, non-linearity, implicit formats, and high computational costs. The objective of this work is to develop a methodology to model equality constraints and a numerical procedure to solve a RBDO problem with equality constraints. Equality constraints are classified into demand-based type and physics-based type. A sequential optimization and reliability analysis strategy is used to solve RBDO with physics-based equality constraints. The first-order reliability method is employed for reliability analysis. The proposed method is illustrated by a mathematical example and a two-member frame design problem. Copyright © 2007 John Wiley & Sons, Ltd. [source] The Effects of the Women, Infants, and Children's Supplemental Food Program on Dentally Related Medicaid ExpendituresJOURNAL OF PUBLIC HEALTH DENTISTRY, Issue 2 2004Jessica Y. Lee DDS Abstract Objective: This study estimates the effects of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) on dentally related Medicaid expenditures for young children. Methods: We used a five-year cohort study design to compare dentally related Medicaid expenditures for children enrolled in WIC versus those not enrolled for each year of life up to age 5 years. There were 49,795 children born in North Carolina in 1992 who met the inclusion criteria for the study. Their birth records were linked to Medicaid enrollment and claims files, WIC master files, and the Area Resource File. Our analysis strategy included a logit and OLS two-part model with CPI dollar adjustments. Results: Children who participated in WIC at ages 1 and 2 years had significantly less dentally related expenditures than those who did not participate. WIC participation at age 3 years did not have a significant effect. Fewer WIC children received dental care under general anesthesia than non-WIC children. Conclusions: The WIC program has the potential for decreasing dentally related costs to the Medicaid program, while increasing use of dental services. [source] | ||||||||||||||||