Validation of a Cost-Efficient Multi-Purpose SNP Panel for Disease Based Research

BACKGROUND: Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA "barcoding" to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies. PRINCIPAL FINDINGS: Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the "barcode." Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel. CONCLUSION: The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists

NSU Convergence Insufficiency Treatment Trial-Reading Study (CITT-RS): Design and Methods

Background. Convergence insufficiency (CI), a common condition in school children, is often associated with symptoms such as frequent loss of place, loss of concentration, having to re-read, reading slowly, trouble remembering what was read, sleepiness, blurred vision, diplopia, headaches, and/or eyestrain. A recently completed randomized clinical trial demonstrated that treatment for convergence insufficiency resulted in significant decreases for the following behaviors: “difficulty completing assignments at school,” “difficulty completing homework,” and “fails to give attention to details or makes careless mistakes in schoolwork or homework.” The question is whether these changes lead to an improvement in reading performance. This presentation describes the design and methodology of the Convergence Insufficiency Treatment Trial (CITT-RS), is a multi-center study designed to provide pilot data about the association between CI and reading, attention, quality of life and the effectiveness of office-based vergence accommodative therapy in improving reading performance of children with symptomatic CI. Methods. There are two parts to CITTRS: CITT-RS Study A and CITT-RS Study B. The CITT-RS Study A, will be an assessment of reading, attention, and quality of life in children with symptomatic CI. CITT-RS Study B will be an intervention study to investigate the potential impact of successful treatment of CI on reading fluency. Data Analysis will be based upon data collected at all clinical sites within the CITT-RS study group from the 50 patients. A one-sample t-test will be used to compare the observed mean value of each outcome measure of children with symptomatic CI to published norms. Regression analysis and correlation coefficients will be used to evaluate the relationship between the clinical measures of convergence insufficiency and the reading measures. Results. Enrollment of subjects was completed in Dec 2009. Data collection of enrolled subjects in the intervention phase and at the final outcome session will be completed by June 2010. Conclusions. Features of this pilot study include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, masked outcome examinations, and the CISS score outcome measur

Randomised clinical trial of the effectiveness of base-in prism reading glasses versus placebo reading glasses for symptomatic convergence insufficiency in children

Purpose: To compare base-in prism reading glasses with placebo reading glasses for the treatment of symptomatic convergence insufficiency (CI) in children aged 9 to <18 years. Methods: In a randomised clinical trial, 72 children aged 9 to <18 years with symptomatic CI were assigned to either base-in prism glasses or placebo reading glasses. Symptom level, measured with a quantitative symptom questionnaire (CI Symptom Survey-V15), was the primary outcome measure. Near point of convergence and positive fusional vergence at near were secondary outcomes. Results: The mean (SD) CI Symptom Survey score decreased (that is, less symptomatic) in both groups (base-in prism glasses from 31.6 (10.4) to 16.5 (9.2); placebo glasses from 28.4 (8.8) to 17.5 (12.3)). The change in the CI Symptom Survey scores (p = 0.33), near point of convergence (p = 0.91), and positive fusional vergence (p = 0.59) were not significantly different between the two groups after 6 weeks of wearing glasses. Conclusions: Base-in prism reading glasses were found to be no more effective in alleviating symptoms, improving the near point of convergence, or improving positive fusional vergence at near than placebo reading glasses for the treatment of children aged 9 to <18 years with symptomatic CI