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Statistical Screening Method for Genetic Factors Influencing Susceptibility to Common Diseases in a Two-Stage Genome-Wide Association Study

  • Yasunori Sato , Nan Laird , Hideki Suganami , Chikuma Hamada , Naoto Niki , Isao Yoshimura and Teruhiko Yoshida
Published/Copyright: November 4, 2009
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Statistical Applications in Genetics and Molecular Biology
From the journal Statistical Applications in Genetics and Molecular Biology Volume 8 Issue 1

A genome-wide association study (GWAS) is a standard strategy for detecting disease susceptibility genes, despite unsettled controversies on many aspects, including optimal study design and statistical analysis. As for study design, a two-stage design has been applied to maximize cost-effectiveness. However, there has been little consensus on appropriate statistical analysis for two-stage design. Thereby perplexing the researchers as to which statistical measures should be applied at the first stage, and how to determine the significance level of the differences at the second stage. Here, using simulation studies, we compared statistical operating characteristics of the screening in a two-stage GWAS by taking into consideration the proper balance of false-positive and false-negative error. As a result, the lower bound of confidence interval for odds ratios is recommended as the first stage measure, and then the second stage criteria should primarily depend on the purpose of the genome screen or its role in the overall gene-hunting scheme. Based on the simulation study, we suggest rules of thumb about which statistics to use in a given situation. An application of all operating characteristics of the screening method to an actual GWAS for gastric cancer illustrates the practical relevance of our discussion.

Keywords: single nucleotide polymorphisms (SNPs); gastric cancer susceptibility genes; false discovery rate (FDR); statistical screening method
Published Online: 2009-11-4

©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston

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  3. Orthology-Based Multilevel Modeling of Differentially Expressed Mouse and Human Gene Pairs
  4. Sequential Analysis for Microarray Data Based on Sensitivity and Meta-Analysis
  5. Dimension Reduction of Microarray Data in the Presence of a Censored Survival Response: A Simulation Study
  6. A Nonlinear Mixed-Effects Model for Estimating Calibration Intervals for Unknown Concentrations in Two-Color Microarray Data with Spike-Ins
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https://doi.org/10.2202/1544-6115.1490
Keywords for this article
single nucleotide polymorphisms (SNPs); gastric cancer susceptibility genes; false discovery rate (FDR); statistical screening method

Articles in the same Issue

  1. Article
  2. Sparse Canonical Correlation Analysis with Application to Genomic Data Integration
  3. Orthology-Based Multilevel Modeling of Differentially Expressed Mouse and Human Gene Pairs
  4. Sequential Analysis for Microarray Data Based on Sensitivity and Meta-Analysis
  5. Dimension Reduction of Microarray Data in the Presence of a Censored Survival Response: A Simulation Study
  6. A Nonlinear Mixed-Effects Model for Estimating Calibration Intervals for Unknown Concentrations in Two-Color Microarray Data with Spike-Ins
  7. Composite Likelihood Modeling of Neighboring Site Correlations of DNA Sequence Substitution Rates
  8. A Multiple Testing Approach to High-Dimensional Association Studies with an Application to the Detection of Associations between Risk Factors of Heart Disease and Genetic Polymorphisms
  9. Hypothesis Tests for Point-Mass Mixture Data with Application to `Omics Data with Many Zero Values
  10. Inferring Dynamic Genetic Networks with Low Order Independencies
  11. Normalization Method for Transcriptional Studies of Heterogeneous Samples - Simultaneous Array Normalization and Identification of Equivalent Expression
  12. A Bayesian Analysis Strategy for Cross-Study Translation of Gene Expression Biomarkers
  13. Modified FDR Controlling Procedure for Multi-Stage Analyses
  14. Detecting Outlier Samples in Microarray Data
  15. Survival Analysis with High-Dimensional Covariates: An Application in Microarray Studies
  16. Two-Stage Model-Based Clustering for Liquid Chromatography Mass Spectrometry Data Analysis
  17. Score Statistics for Mapping Quantitative Trait Loci
  18. Impact of Population Stratification on Family-Based Association Tests with Longitudinal Measurements
  19. A Multilocus Model for Constructing a Linkage Disequilibrium Map in Human Populations
  20. Testing of Chromosomal Clumping of Gene Properties
  21. Balanced Gradient Boosting from Imbalanced Data for Clinical Outcome Prediction
  22. Univariate Shrinkage in the Cox Model for High Dimensional Data
  23. Multilevel Comparison of Dendrograms: A New Method with an Application for Genetic Classifications
  24. Weighted Multiple Hypothesis Testing Procedures
  25. Incorporating Duplicate Genotype Data into Linear Trend Tests of Genetic Association: Methods and Cost-Effectiveness
  26. Increase of Rejection Rate in Case-Control Studies with the Differential Genotyping Error Rates
  27. A Parametric Model for Analyzing Anticipation in Genetically Predisposed Families
  28. Bayesian Unsupervised Learning with Multiple Data Types
  29. Extensions of Sparse Canonical Correlation Analysis with Applications to Genomic Data
  30. A Non-Homogeneous Hidden-State Model on First Order Differences for Automatic Detection of Nucleosome Positions
  31. Adaptive Transmission Disequilibrium Test for Family Trio Design
  32. Model Selection Based on FDR-Thresholding Optimizing the Area under the ROC-Curve
  33. Estimation of Selection Intensity under Overdominance by Bayesian Methods
  34. A Multivariate Growth Curve Model for Ranking Genes in Replicated Time Course Microarray Data
  35. Rotation Testing in Gene Set Enrichment Analysis for Small Direct Comparison Experiments
  36. Ancestral Recombination Graphs under Non-Random Ascertainment, with Applications to Gene Mapping
  37. Prediction of Motifs Based on a Repeated-Measures Model for Integrating Cross-Species Sequence and Expression Data
  38. Identifying Individuals in a Complex Mixture of DNA with Unknown Ancestry
  39. A Statistical Model for Genetic Mapping of Viral Infection by Integrating Epidemiological Behavior
  40. Calculating Asymptotic Significance Levels of the Constrained Likelihood Ratio Test with Application to Multivariate Genetic Linkage Analysis
  41. Modeling Dependence in Methylation Patterns with Application to Ovarian Carcinomas
  42. M-quantile Regression Analysis of Temporal Gene Expression Data
  43. MC-Normalization: A Novel Method for Dye-Normalization of Two-Channel Microarray Data
  44. Characterizing the D2 Statistic: Word Matches in Biological Sequences
  45. Transmission Disequilibrium Test Power and Sample Size in the Presence of Locus Heterogeneity
  46. A Regularized Regression Approach for Dissecting Genetic Conflicts that Increase Disease Risk in Pregnancy
  47. Statistical Screening Method for Genetic Factors Influencing Susceptibility to Common Diseases in a Two-Stage Genome-Wide Association Study
  48. A Unified Mixed Effects Model for Gene Set Analysis of Time Course Microarray Experiments
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