Home Adaptive Transmission Disequilibrium Test for Family Trio Design
Article
Licensed
Unlicensed Requires Authentication

Adaptive Transmission Disequilibrium Test for Family Trio Design

  • Min Yuan , Xin Tian , Gang Zheng and Yaning Yang
Published/Copyright: June 23, 2009
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Statistical Applications in Genetics and Molecular Biology
From the journal Statistical Applications in Genetics and Molecular Biology Volume 8 Issue 1

The transmission disequilibrium test (TDT) is a standard method to detect association using family trio design. It is optimal for an additive genetic model. Other TDT-type tests optimal for recessive and dominant models have also been developed. Association tests using family data, including the TDT-type statistics, have been unified to a class of more comprehensive and flexable family-based association tests (FBAT). TDT-type tests have high efficiency when the genetic model is known or correctly specified, but may lose power if the model is mis-specified. Hence tests that are robust to genetic model mis-specification yet efficient are preferred. Constrained likelihood ratio test (CLRT) and MAX-type test have been shown to be efficiency robust. In this paper we propose a new efficiency robust procedure, referred to as adaptive TDT (aTDT). It uses the Hardy-Weinberg disequilibrium coefficient to identify the potential genetic model underlying the data and then applies the TDT-type test (or FBAT for general applications) corresponding to the selected model. Simulation demonstrates that aTDT is efficiency robust to model mis-specifications and generally outperforms the MAX test and CLRT in terms of power. We also show that aTDT has power close to, but much more robust, than the optimal TDT-type test based on a single genetic model. Applications to real and simulated data from Genetic Analysis Workshop (GAW) illustrate the use of our adaptive TDT.

Keywords: adaptive TDT; conditional power; efficiency robustness; genetic model selection; Hardy-Weinberg disequilibrium; MAX-type tests; TDT-type tests; FBAT; constrained likelihood ratio test
Published Online: 2009-6-23

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

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
https://doi.org/10.2202/1544-6115.1451
Keywords for this article
adaptive TDT; conditional power; efficiency robustness; genetic model selection; Hardy-Weinberg disequilibrium; MAX-type tests; TDT-type tests; FBAT; constrained likelihood ratio test

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
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 11.9.2025 from https://www.degruyterbrill.com/document/doi/10.2202/1544-6115.1451/html
Scroll to top button