scholarly journals Marker-Trait Complete Analysis

2019 ◽  
Author(s):  
Yi-Hui Zhou ◽  
Paul Gallins ◽  
Fred Wright
Keyword(s):  
Multiple Testing ◽  
Asymptotic Methods ◽  
Conditional Inference ◽  
Complete Analysis ◽  
Eqtl Analysis ◽  
Conditional Moments ◽  
Association Testing ◽  
Fast Screening ◽  
Multivariate Normal Approximation ◽  
Continuous Phenotype

1AbstractA recurring problem in genomics involves testing association of one or more traits of interest to multiple genomic features. Feature-trait squared correlations r2 are commonly-used statistics, sensitive to trend associations. It is often of interest to perform testing across collections {r2} over markers and/or traits using both maxima and sums. However, both trait-trait correlations and marker-marker correlations may be strong and must be considered. The primary tools for multiple testing suffer from various shortcomings, including p-value inaccuracies due to asymptotic methods that may not be applicable. Moreover, there is a lack of general tools for fast screening and follow-up of regions of interest.To address these difficulties, we propose the MTCA approach, for Marker-Trait Complete Analysis. MTCA encompasses a large number of existing approaches, and provides accurate p-values over markers and traits for maxima and sums of r2 statistics. MTCA uses the conditional inference implicit in permutation as a motivational frame-work, but provides an option for fast screening with two novel tools: (i) a multivariate-normal approximation for the max statistic, and (ii) the concept of eigenvalue-conditional moments for the sum statistic. We provide examples for gene-based association testing of a continuous phenotype and cis-eQTL analysis, but MTCA can be applied in a much wider variety of settings and platforms.

scholarly journals Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura

Cephalalgia ◽  
2013 ◽  
Vol 33 (7) ◽  
pp. 469-482 ◽  
Author(s):  
Kathryn A Roecklein ◽  
Ann I Scher ◽  
Albert Smith ◽  
Tamara Harris ◽  
Gudny Eiriksdottir ◽  
...  
Keyword(s):  
Migraine With Aura ◽  
Multiple Testing ◽  
Haplotype Analysis ◽  
Methylenetetrahydrofolate Reductase ◽  
Population Based ◽  
Methionine Synthase ◽  
Association Testing ◽  
Methionine Synthase Reductase ◽  
Increased Risk ◽  
Genes Encoding

Aims The C677T variant in the methylenetetrahydrofolate reductase ( MTHFR; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include methionine synthase ( MTR; EC 2.1.1.13) and methionine synthase reductase ( MTRR; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR, MTR, and MTRR. Methods Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache ( n = 367), migraine without aura ( n = 85), migraine with aura ( n = 167), and no headache ( n = 1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNP and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing. Results Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing. Conclusions These results suggest that MTRR variants may protect against migraine with aura in an older population.

scholarly journals Joint variable selection and network modeling for detecting eQTLs

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuan Cao ◽  
Lili Ding ◽  
Tesfaye B. Mersha
Keyword(s):  
Variable Selection ◽  
Multiple Testing ◽  
Bayes Factor ◽  
Graph Model ◽  
Real Data ◽  
Bayesian Regression ◽  
Joint Estimation ◽  
Eqtl Analysis ◽  
Multiple Testing Correction ◽  
Joint Variable

AbstractIn this study, we conduct a comparison of three most recent statistical methods for joint variable selection and covariance estimation with application of detecting expression quantitative trait loci (eQTL) and gene network estimation, and introduce a new hierarchical Bayesian method to be included in the comparison. Unlike the traditional univariate regression approach in eQTL, all four methods correlate phenotypes and genotypes by multivariate regression models that incorporate the dependence information among phenotypes, and use Bayesian multiplicity adjustment to avoid multiple testing burdens raised by traditional multiple testing correction methods. We presented the performance of three methods (MSSL – Multivariate Spike and Slab Lasso, SSUR – Sparse Seemingly Unrelated Bayesian Regression, and OBFBF – Objective Bayes Fractional Bayes Factor), along with the proposed, JDAG (Joint estimation via a Gaussian Directed Acyclic Graph model) method through simulation experiments, and publicly available HapMap real data, taking asthma as an example. Compared with existing methods, JDAG identified networks with higher sensitivity and specificity under row-wise sparse settings. JDAG requires less execution in small-to-moderate dimensions, but is not currently applicable to high dimensional data. The eQTL analysis in asthma data showed a number of known gene regulations such as STARD3, IKZF3 and PGAP3, all reported in asthma studies. The code of the proposed method is freely available at GitHub (https://github.com/xuan-cao/Joint-estimation-for-eQTL).

scholarly journals Insight into genetic regulation of miRNA in mouse brain

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Gordon Kordas ◽  
Pratyaydipta Rudra ◽  
Audrey Hendricks ◽  
Laura Saba ◽  
Katerina Kechris
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Bayesian Network ◽  
Brain Tissue ◽  
Mirna Expression ◽  
Multiple Testing ◽  
Eqtl Analysis ◽  
Mirna Regulation ◽  
Expression Levels ◽  
Insight Into

Abstract Background micro RNA (miRNA) are important regulators of gene expression and may influence phenotypes and disease traits. The connection between genetics and miRNA expression can be determined through expression quantitative loci (eQTL) analysis, which has been extensively used in a variety of tissues, and in both human and model organisms. miRNA play an important role in brain-related diseases, but eQTL studies of miRNA in brain tissue are limited. We aim to catalog miRNA eQTL in brain tissue using miRNA expression measured on a recombinant inbred mouse panel. Because samples were collected without any intervention or treatment (naïve), the panel allows characterization of genetic influences on miRNAs’ expression levels. We used brain RNA expression levels of 881 miRNA and 1416 genomic locations to identify miRNA eQTL. To address multiple testing, we employed permutation p-values and subsequent zero permutation p-value correction. We also investigated the underlying biology of miRNA regulation using additional analyses, including hotspot analysis to search for regions controlling multiple miRNAs, and Bayesian network analysis to identify scenarios where a miRNA mediates the association between genotype and mRNA expression. We used addiction related phenotypes to illustrate the utility of our results. Results Thirty-eight miRNA eQTL were identified after appropriate multiple testing corrections. Ten of these miRNAs had target genes enriched for brain-related pathways and mapped to four miRNA eQTL hotspots. Bayesian network analysis revealed four biological networks relating genetic variation, miRNA expression and gene expression. Conclusions Our extensive evaluation of miRNA eQTL provides valuable insight into the role of miRNA regulation in brain tissue. Our miRNA eQTL analysis and extended statistical exploration identifies miRNA candidates in brain for future study.

scholarly journals Co-expression analysis reveals interpretable gene modules controlled by trans-acting genetic variants

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Liis Kolberg ◽  
Nurlan Kerimov ◽  
Hedi Peterson ◽  
Kaur Alasoo
Keyword(s):  
Gene Expression ◽  
Multiple Testing ◽  
Disease Onset ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Cell Types ◽  
Functional Enrichment ◽  
Eqtl Analysis ◽  
Cellular Processes ◽  
Causal Processes

Understanding the causal processes that contribute to disease onset and progression is essential for developing novel therapies. Although trans-acting expression quantitative trait loci (trans-eQTLs) can directly reveal cellular processes modulated by disease variants, detecting trans-eQTLs remains challenging due to their small effect sizes. Here, we analysed gene expression and genotype data from six blood cell types from 226 to 710 individuals. We used co-expression modules inferred from gene expression data with five methods as traits in trans-eQTL analysis to limit multiple testing and improve interpretability. In addition to replicating three established associations, we discovered a novel trans-eQTL near SLC39A8 regulating a module of metallothionein genes in LPS-stimulated monocytes. Interestingly, this effect was mediated by a transient cis-eQTL present only in early LPS response and lost before the trans effect appeared. Our analyses highlight how co-expression combined with functional enrichment analysis improves the identification and prioritisation of trans-eQTLs when applied to emerging cell-type-specific datasets.

scholarly journals Impact of Genetic Ancestry on Prognostic Biomarkers in Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3208
Author(s):  
Daniel A. Rodriguez ◽  
Margaret I. Sanchez ◽  
Christina L. Decatur ◽  
Zelia M. Correa ◽  
Eden R. Martin ◽  
...  
Keyword(s):  
Native American ◽  
Uveal Melanoma ◽  
Multiple Testing ◽  
Genetic Ancestry ◽  
Prognostic Biomarkers ◽  
European Ancestry ◽  
Genetic Admixture ◽  
Eqtl Analysis ◽  
Immune Genes ◽  
Global And Local

Uveal melanoma (UM) is the most common cancer of the eye and leads to metastatic death in up to half of patients. Genomic prognostic biomarkers play an important role in clinical management in UM. However, research has been conducted almost exclusively in patients of European descent, such that the association between genetic admixture and prognostic biomarkers is unknown. In this study, we compiled 1381 control genomes from West African, European, East Asian, and Native American individuals, assembled a bioinformatic pipeline for assessing global and local ancestry, and performed an initial pilot study of 141 UM patients from our international referral center that manages many admixed individuals. Global and local estimates were associated with genomic prognostic determinants. Expression quantitative trait loci (eQTL) analysis was performed on variants found in segments. Globally, after correction for multiple testing, no prognostic variable was significantly enriched in a given ancestral group. However, there was a trend suggesting an increased proportion of European ancestry associated with expression of the PRAME oncogene (q = 0.06). Locally enriched European haplotypes were associated with the poor prognosis class 2 gene expression profile and with genes involved in immune regulation (q = 4.7 × 10−11). These findings reveal potential influences of genetic ancestry on prognostic variables, implicate immune genes in prognostic differences based on ancestry, and provide a basis for future studies of admixed patients with UM using rigorous genetic ancestry methodology.

From Finite Sample to Asymptotic Methods in Statistics

2009 ◽  
Author(s):  
Pranab K. Sen ◽  
Julio M. Singer ◽  
Antonio C. Pedroso de Lima
Keyword(s):  
Asymptotic Methods ◽  
Finite Sample

TOURIST BUSINESS DEVELOPMENT IN UKRAINE

2019 ◽  
pp. 39-46
Author(s):  
Stefania Mosiuk ◽  
Igor Mosiuk ◽  
Vladimir Mosiuk
Keyword(s):  
National Economy ◽  
Methodological Approach ◽  
Business Development ◽  
Tourism Industry ◽  
The State ◽  
Complete Analysis ◽  
Resource Potential ◽  
The World ◽  
Potential Resource ◽  
Favorable Conditions

The purpose of the article is to analyze and substantiate the development of tourism business in Ukraine as a priority component of the national economy. The methodology of this study is to use analytical, spatial, geographical, cultural and other methods. This methodological approach provided an opportunity to carry out a complete analysis of the state of the tourism industry of the state and to draw some conclusions.The scientific novelty lies in the coverage of the real and potential resource potential for the development of the recreational and tourism sphere in Ukraine, detailing the measures for the country ‘s entry into the world tourist market. Conclusions. Analyzing the state and prospects of tourism business development in Ukraine, it should be noted that this industry is one of the priority areas for improving the economy of the country. Historical, cultural – ethnographic, gastronomic, sanatorium and resort potentials of the country will lead the country into world leaders of the tourism industry when creating favorable conditions for investment and proper marketing.

Dosimetry and optimization in digital radiography based on the contrast-detail resolution

2018 ◽  
Vol 6 (3) ◽  
Author(s):  
Wilson Otto Gomes Batista ◽  
Alexandre Gomes De Carvalho
Keyword(s):  
Image Quality ◽  
Inverse Image ◽  
Point Of View ◽  
Complete Analysis ◽  
Portable Devices ◽  
Evaluation Tool ◽  
Air Kerma ◽  
Direct Radiography ◽  
Definition Of ◽  
Entrance Surface Air Kerma

Contrast-detail (C-D) curves are useful in evaluating the radiographic image quality in a global way. The objective of the present study was to obtain the C-D curves and the inverse image quality figure. Both of these parameters were used as an evaluation tool for abdominal and chest imaging protocols. The C-D curves were obtained with the phantom CDRAD 2.0 in computerized radiography and the direct radiography systems (including portable devices). The protocols were 90 and 102 kV in the range of 2 to 20 mAs for the chest and 80 kV in the range of 10 to 80 mAs for the abdomen. The incident air kerma values were evaluated with a solid state sensor. The analysis of these C-D curves help to identify which technique would allow a lower value of the entrance surface air kerma, Ke, while maintaining the image quality from the point of view of C-D detectability. The results showed that the inverse image quality figure, IQFinv, varied little throughout the range of mAs, while the value of Ke varied linearly directly with the mAs values. Also, the complete analysis of the curves indicated that there was an increase in the definition of the details with increasing mAs. It can be concluded that, in the transition phase for the use of the new receptors, it is necessary to evaluate and adjust the practised protocols to ensure, at a minimum, the same levels of the image quality, taking into account the aspects of the radiation protection of the patient.

Use of Asymptotic Methods in Studying the Temperature Field in the Operating Well

2006 ◽  
Vol 37 (5) ◽  
pp. 407-419
Author(s):  
A. I. Filippov ◽  
P. N. Mikhailov ◽  
K. A. Filippov
Keyword(s):  
Temperature Field ◽  
Asymptotic Methods

Degenerate Diffusion Operators Arising in Population Biology (AM-185)

2017 ◽  
Author(s):  
Charles L. Epstein ◽  
Rafe Mazzeo
Keyword(s):  
Adjoint Operator ◽  
Integral Kernel ◽  
Mathematical Finance ◽  
Elliptic Operators ◽  
Complete Analysis ◽  
Time Behavior ◽  
Degenerate Elliptic Operators ◽  
Regularity Properties ◽  
Degenerate Elliptic ◽  
Mathematical Foundations

This book provides the mathematical foundations for the analysis of a class of degenerate elliptic operators defined on manifolds with corners, which arise in a variety of applications such as population genetics, mathematical finance, and economics. The results discussed in this book prove the uniqueness of the solution to the martingale problem and therefore the existence of the associated Markov process. The book uses an “integral kernel method” to develop mathematical foundations for the study of such degenerate elliptic operators and the stochastic processes they define. The precise nature of the degeneracies of the principal symbol for these operators leads to solutions of the parabolic and elliptic problems that display novel regularity properties. Dually, the adjoint operator allows for rather dramatic singularities, such as measures supported on high codimensional strata of the boundary. The book establishes the uniqueness, existence, and sharp regularity properties for solutions to the homogeneous and inhomogeneous heat equations, as well as a complete analysis of the resolvent operator acting on Hölder spaces. It shows that the semigroups defined by these operators have holomorphic extensions to the right half plane. The book also demonstrates precise asymptotic results for the long-time behavior of solutions to both the forward and backward Kolmogorov equations.

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