A New Explained-Variance Based Genetic Risk Score for Predictive Modeling of Disease Risk
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Ronglin Che
Abstract
The goal of association mapping is to identify genetic variants that predict disease, and as the field of human genetics matures, the number of successful association studies is increasing. Many such studies have shown that for many diseases, risk is explained by a reasonably large number of variants that each explains a very small amount of disease risk. This is prompting the use of genetic risk scores in building predictive models, where information across several variants is combined for predictive modeling. In the current study, we compare the performance of four previously proposed genetic risk score methods and present a new method for constructing genetic risk score that incorporates explained variance information. The methods compared include: a simple count Genetic Risk Score, an odds ratio weighted Genetic Risk Score, a direct logistic regression Genetic Risk Score, a polygenic Genetic Risk Score, and the new explained variance weighted Genetic Risk Score. We compare the methods using a wide range of simulations in two steps, with a range of the number of deleterious single nucleotide polymorphisms (SNPs) explaining disease risk, genetic modes, baseline penetrances, sample sizes, relative risks (RR) and minor allele frequencies (MAF). Several measures of model performance were compared including overall power, C-statistic and Akaike’s Information Criterion. Our results show the relative performance of methods differs significantly, with the new explained variance weighted GRS (EV-GRS) generally performing favorably to the other methods.
©2012 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Articles in the same Issue
- Article
- A New Explained-Variance Based Genetic Risk Score for Predictive Modeling of Disease Risk
- Hessian Calculation for Phylogenetic Likelihood based on the Pruning Algorithm and its Applications
- Cluster-Localized Sparse Logistic Regression for SNP Data
- How to analyze many contingency tables simultaneously in genetic association studies
- Incorporating the Empirical Null Hypothesis into the Benjamini-Hochberg Procedure
- Estimating the Number of One-step Beneficial Mutations
- Testing clonality of three and more tumors using their loss of heterozygosity profiles
- Correction for Founder Effects in Host-Viral Association Studies via Principal Components
- A Non-Homogeneous Dynamic Bayesian Network with Sequentially Coupled Interaction Parameters for Applications in Systems and Synthetic Biology
- An Integrated Hierarchical Bayesian Model for Multivariate eQTL Mapping
- A Novel and Fast Normalization Method for High-Density Arrays
- Performance of MAX Test and Degree of Dominance Index in Predicting the Mode of Inheritance
- A Bayesian autoregressive three-state hidden Markov model for identifying switching monotonic regimes in Microarray time course data
- QTL Mapping Using a Memetic Algorithm with Modifications of BIC as Fitness Function
- Computing Posterior Probabilities for Score-based Alignments Using ppALIGN
Articles in the same Issue
- Article
- A New Explained-Variance Based Genetic Risk Score for Predictive Modeling of Disease Risk
- Hessian Calculation for Phylogenetic Likelihood based on the Pruning Algorithm and its Applications
- Cluster-Localized Sparse Logistic Regression for SNP Data
- How to analyze many contingency tables simultaneously in genetic association studies
- Incorporating the Empirical Null Hypothesis into the Benjamini-Hochberg Procedure
- Estimating the Number of One-step Beneficial Mutations
- Testing clonality of three and more tumors using their loss of heterozygosity profiles
- Correction for Founder Effects in Host-Viral Association Studies via Principal Components
- A Non-Homogeneous Dynamic Bayesian Network with Sequentially Coupled Interaction Parameters for Applications in Systems and Synthetic Biology
- An Integrated Hierarchical Bayesian Model for Multivariate eQTL Mapping
- A Novel and Fast Normalization Method for High-Density Arrays
- Performance of MAX Test and Degree of Dominance Index in Predicting the Mode of Inheritance
- A Bayesian autoregressive three-state hidden Markov model for identifying switching monotonic regimes in Microarray time course data
- QTL Mapping Using a Memetic Algorithm with Modifications of BIC as Fitness Function
- Computing Posterior Probabilities for Score-based Alignments Using ppALIGN
