Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes.
Estimation of statistical power and sample size is a key aspect of experimental design.However, in metabolic phenotyping, there is currently no accepted approach for these tasks, in large part due to the unknown nature of the expected effect. In such hypothesis free science, neither the number or class of important analytes, nor the effect size are known a priori. We introduce a new approach, based on multivariate simulation, which deals effectively with the highly correlated structure and high-dimensionality of metabolic phenotyping data. First, a large data set is simulated based on the characteristics of a pilot study investigating a given biomedical issue. An effect of a given size, corresponding either to a discrete (classification) or continuous (regression) outcome is then added. Different sample sizes are modeled by randomly selecting data sets of various sizes from the simulated data.We investigate different methods for effect detection, including univariate and multivariate techniques. Our framework allows us to investigate the complex relationship between sample size, power and effect size for real multivariate data sets. elegans.
The stability of tetrahydrofuran (THF)-based electrolytes toward bulk and electroplated Li has been assessed. Those electrolytes incorporating LiAsF6 were least reactive to Li at elevated temperature and gave the best cycling efficiencies. These efficiencies could be further improved by aging the electrolyte at 71~ and by the addition of O~ or N2. Conversely, CO2 degraded the performance of the secondary Li electrode. Small quantities of Na + and the variation of inert metal substrate had little, if any, effect on cycling efficiencies. Preelectrolyzing the electrolyte improved the cycling characteristics initially, but lengthy preelectrolysis resulted in electrolyte degradation. A recontact phenomenon, whereby previously isolated Li is recouped in subsequent cycles, was noted. The intervention of films is proposed to account for these observations. * Electrochemical Society Active Member.
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