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Transmission Disequilibrium Test Power and Sample Size in the Presence of Locus Heterogeneity

  • Chuanwen Chen , Guang Yang , Steven Buyske , Tara Matise , Stephen J Finch and Derek Gordon
Published/Copyright: October 8, 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

Locus heterogeneity is one of the most important issues in gene mapping and can cause significant reductions in statistical power for gene mapping, yet no research to date has provided power and sample size calculations for family-based association methods in the presence of locus heterogeneity. The purpose of this research is three-fold: (i) to provide an analytic solution to the incorporation of locus heterogeneity into power and sample size calculations for the TDT statistic; (ii) to verify our analytic solution with simulations; and (iii) to study how different factors affect sample size requirement for the TDT in the presence of locus heterogeneity.The detection of association in the presence of locus heterogeneity requires a greater sample size than in its absence. This increase is independent of the prevalence of the disease. In addition, as the proportion of families unlinked to the disease locus increases, the sample size necessary to maintain constant power increases. Finally, as the effect size of the disease locus increases, the sample size necessary to detect association decreases in the presence of locus heterogeneity. We provide freely available software that can perform these calculations.

Keywords: mixture; noncentrality parameter; family-based association
Published Online: 2009-10-8

©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
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  5. Dimension Reduction of Microarray Data in the Presence of a Censored Survival Response: A Simulation Study
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https://doi.org/10.2202/1544-6115.1501
Keywords for this article
mixture; noncentrality parameter; family-based association

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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