Browsing by Author "Li, YJ"

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    Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study.
    (BMC Genet, 2005-12-30) Li, YJ; Martin, ER; Zhang, L; Allen, AS
    Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted.
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    Associations between Features of External Ventricular Drain Management, Disposition, and Shunt Dependence
    (Journal of Neuroanaesthesiology and Critical Care) Engel, C; Faulkner, AL; Van Wyck, DW; Zomorodi, AR; King, NKK; Williamson Taylor, RA; Hailey, CE; Umeano, OA; McDonagh, DL; Li, YJ; James, ML
    Abstract Background In the United States, nearly 25,000 patients annually undergo percutaneous ventriculostomy for the management of increased intracranial pressure with little consensus on extraventricular drain management. To characterize relationships between external ventricular drain management, permanent ventriculoperitoneal shunt placement, and hospital disposition, we hypothesized that patients requiring extended drainage would have greater association with ventriculoperitoneal shunt placement and unfavorable disposition. Methods Adult patients admitted to the Duke University Hospital Neuroscience Intensive Care Unit between 2008 and 2010 with extraventricular drains were analyzed. A total of 115 patient encounters were assessed to determine relative impact of age, sex, days of extraventricular placement, weaning attempts, cerebrospinal fluid drainage volumes, Glasgow Coma Scale, and physician’s experience on disposition at discharge and ventriculoperitoneal shunt placement. Univariate logistic regression was first used to test the effect of each variable on the outcome, followed by backward selection to determine a final multivariable logistic regression. Variables in the final model meeting p < 0.05 were declared as significant factors for the outcome. Results Increased extraventricular drain duration (odds ratio [OR] = 1.17, confidence interval [CI] = 1.05–1.30, p = 0.0049) was associated with ventriculoperitoneal shunt placement, while older age (OR = 1.05, CI = 1.02–1.08, p = 0.0027) and less physician extraventricular drain management experience (OR = 4.04, CI = 1.67–9.79, p = 0.0020) were associated with unfavorable disposition. Conclusion In a small cohort, exploratory analyses demonstrate potentially modifiable factors are associated with important clinical outcomes. These findings warrant further study to refine how such factors affect patient outcomes.
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    Blood Pressure-Lowering Mechanisms of the DASH Dietary Pattern.
    (J Nutr Metab, 2012) Lin, PH; Allen, JD; Li, YJ; Yu, M; Lien, LF; Svetkey, LP
    Potential blood pressure- (BP-) lowering mechanisms of the DASH dietary pattern were measured in 20 unmedicated hypertensive adults in a controlled feeding study. At screening, participants averaged 44.3 ± 7.8 years, BMI 33.9 ± 6.6 Kg/m(2), and BP 144.2 ± 9.38/88.5 ± 6.03 mmHg. All consumed a control diet for one week, then were randomized to control or DASH for another two weeks (week one and two). With DASH, but not controls, SBP fell by 10.65 ± 12.89 (P = 0.023) and 9.60 ± 11.23 (P = 0.039) mmHg and DBP by 5.95 ± 8.01 (P = 0.069) and 8.60 ± 9.13 mmHg (P = 0.011) at the end of week one and two, respectively. Univariate regressions showed that changes in urinary sodium/potassium ratio (β = 1.99) and plasma renin activity (β = -15.78) and percent change in plasma nitrite after hyperemia were associated with SBP changes at week one (all P < 0.05). Plasma nitrite following hyperemia showed a treatment effect (P = 0.014) and increased at week two (P = 0.001). Pulse wave velocity decreased over time with DASH (trend P = 0.019), and reached significance at week two (P = 0.026). This response may be mediated by an improvement in upregulation of nitric oxide bioavailability. Early natriuresis and reductions in oxidative stress cannot be ruled out. Future studies are needed to verify these findings, assess the possibility of earlier effects, and examine other potential mediators.
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    Common Genetic Variants near the Brittle Cornea Syndrome Locus ZNF469 Influence the Blinding Disease Risk Factor Central Corneal Thickness
    (PLoS Genetics, 2010-05-13) Lu, Y; Dimasi, DP; Hysi, PG; Hewitt, AW; Burdon, KP; Toh, T; Ruddle, JB; Li, YJ; Mitchell, P; Healey, PR; Montgomery, GW; Hansell, N; Spector, TD; Martin, NG; Young, TL; Hammond, CJ; Macgregor, S; Craig, JE; Mackey, DA
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    Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays.
    (Nucleic Acids Res, 2010-05) Dellinger, AE; Saw, SM; Goh, LK; Seielstad, M; Young, TL; Li, YJ
    Determination of copy number variants (CNVs) inferred in genome wide single nucleotide polymorphism arrays has shown increasing utility in genetic variant disease associations. Several CNV detection methods are available, but differences in CNV call thresholds and characteristics exist. We evaluated the relative performance of seven methods: circular binary segmentation, CNVFinder, cnvPartition, gain and loss of DNA, Nexus algorithms, PennCNV and QuantiSNP. Tested data included real and simulated Illumina HumHap 550 data from the Singapore cohort study of the risk factors for Myopia (SCORM) and simulated data from Affymetrix 6.0 and platform-independent distributions. The normalized singleton ratio (NSR) is proposed as a metric for parameter optimization before enacting full analysis. We used 10 SCORM samples for optimizing parameter settings for each method and then evaluated method performance at optimal parameters using 100 SCORM samples. The statistical power, false positive rates, and receiver operating characteristic (ROC) curve residuals were evaluated by simulation studies. Optimal parameters, as determined by NSR and ROC curve residuals, were consistent across datasets. QuantiSNP outperformed other methods based on ROC curve residuals over most datasets. Nexus Rank and SNPRank have low specificity and high power. Nexus Rank calls oversized CNVs. PennCNV detects one of the fewest numbers of CNVs.