scholarly journals MCGA: a multi-strategy conditional gene-based association framework integrating with isoform-level expression profiles reveals new susceptible and druggable candidate genes of schizophrenia

2021 ◽  
Author(s):  
Xiangyi Li ◽  
Lin Jiang ◽  
Chao Xue ◽  
Mulin Jun Li ◽  
Miaoxin Li

Linkage disequilibrium and disease-associated variants in non-coding regions make it difficult to distinguish truly associated genes from redundantly associated genes for complex diseases. In this study, we proposed a new conditional gene-based framework called MCGA that leveraged an improved effective chi-squared statistic to control the type I error rates and remove the redundant associations. MCGA initially integrated two conventional strategies to map genetic variants to genes, i.e., mapping a variant to its physically nearby gene and mapping a variant to a gene if the variant is a gene-level expression quantitative trait locus (eQTL) of the gene. We further performed a simulation study and demonstrated that the isoform-level eQTL was more powerful than the gene-level eQTL in the association analysis. Then the third strategy, i.e., mapping a variant to a gene if the variant is an isoform-level eQTL of the gene, was also integrated with MCGA. We applied MCGA to predict the potential susceptibility genes of schizophrenia and found that the potential susceptibility genes identified by MCGA were enriched with many neuronal or synaptic signaling-related terms in the Gene Ontology knowledgebase and antipsychotics-gene interaction terms in the drug-gene interaction database (DGIdb). More importantly, nine susceptibility genes were the target genes of multiple approved antipsychotics in DrugBank. Comparing the susceptibility genes identified by the above three strategies implied that strategy based on isoform-level eQTL could be an important supplement for the other two strategies and help predict more candidate susceptibility isoforms and genes for complex diseases in a multi-tissue context.

2014 ◽  
Vol 53 (05) ◽  
pp. 343-343

We have to report marginal changes in the empirical type I error rates for the cut-offs 2/3 and 4/7 of Table 4, Table 5 and Table 6 of the paper “Influence of Selection Bias on the Test Decision – A Simulation Study” by M. Tamm, E. Cramer, L. N. Kennes, N. Heussen (Methods Inf Med 2012; 51: 138 –143). In a small number of cases the kind of representation of numeric values in SAS has resulted in wrong categorization due to a numeric representation error of differences. We corrected the simulation by using the round function of SAS in the calculation process with the same seeds as before. For Table 4 the value for the cut-off 2/3 changes from 0.180323 to 0.153494. For Table 5 the value for the cut-off 4/7 changes from 0.144729 to 0.139626 and the value for the cut-off 2/3 changes from 0.114885 to 0.101773. For Table 6 the value for the cut-off 4/7 changes from 0.125528 to 0.122144 and the value for the cut-off 2/3 changes from 0.099488 to 0.090828. The sentence on p. 141 “E.g. for block size 4 and q = 2/3 the type I error rate is 18% (Table 4).” has to be replaced by “E.g. for block size 4 and q = 2/3 the type I error rate is 15.3% (Table 4).”. There were only minor changes smaller than 0.03. These changes do not affect the interpretation of the results or our recommendations.


2021 ◽  
pp. 001316442199489
Author(s):  
Luyao Peng ◽  
Sandip Sinharay

Wollack et al. (2015) suggested the erasure detection index (EDI) for detecting fraudulent erasures for individual examinees. Wollack and Eckerly (2017) and Sinharay (2018) extended the index of Wollack et al. (2015) to suggest three EDIs for detecting fraudulent erasures at the aggregate or group level. This article follows up on the research of Wollack and Eckerly (2017) and Sinharay (2018) and suggests a new aggregate-level EDI by incorporating the empirical best linear unbiased predictor from the literature of linear mixed-effects models (e.g., McCulloch et al., 2008). A simulation study shows that the new EDI has larger power than the indices of Wollack and Eckerly (2017) and Sinharay (2018). In addition, the new index has satisfactory Type I error rates. A real data example is also included.


2001 ◽  
Vol 26 (1) ◽  
pp. 105-132 ◽  
Author(s):  
Douglas A. Powell ◽  
William D. Schafer

The robustness literature for the structural equation model was synthesized following the method of Harwell which employs meta-analysis as developed by Hedges and Vevea. The study focused on the explanation of empirical Type I error rates for six principal classes of estimators: two that assume multivariate normality (maximum likelihood and generalized least squares), elliptical estimators, two distribution-free estimators (asymptotic and others), and latent projection. Generally, the chi-square tests for overall model fit were found to be sensitive to non-normality and the size of the model for all estimators (with the possible exception of the elliptical estimators with respect to model size and the latent projection techniques with respect to non-normality). The asymptotic distribution-free (ADF) and latent projection techniques were also found to be sensitive to sample sizes. Distribution-free methods other than ADF showed, in general, much less sensitivity to all factors considered.


2019 ◽  
Vol 14 (2) ◽  
pp. 399-425 ◽  
Author(s):  
Haolun Shi ◽  
Guosheng Yin

2014 ◽  
Vol 38 (2) ◽  
pp. 109-112 ◽  
Author(s):  
Daniel Furtado Ferreira

Sisvar is a statistical analysis system with a large usage by the scientific community to produce statistical analyses and to produce scientific results and conclusions. The large use of the statistical procedures of Sisvar by the scientific community is due to it being accurate, precise, simple and robust. With many options of analysis, Sisvar has a not so largely used analysis that is the multiple comparison procedures using bootstrap approaches. This paper aims to review this subject and to show some advantages of using Sisvar to perform such analysis to compare treatments means. Tests like Dunnett, Tukey, Student-Newman-Keuls and Scott-Knott are performed alternatively by bootstrap methods and show greater power and better controls of experimentwise type I error rates under non-normal, asymmetric, platykurtic or leptokurtic distributions.


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