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BackgroundIdentification of causal SNPs in most genome wide association studies relies on approaches that consider each SNP individually. However, there is a strong correlation structure among SNPs that needs to be taken into account. Hence, increasingly modern computationally expensive regression methods are employed for SNP selection that consider all markers simultaneously and thus incorporate dependencies among SNPs.ResultsWe develop a novel multivariate algorithm for large scale SNP selection using CAR score regression, a promising new approach for prioritizing biomarkers. Specifically, we propose a computationally efficient procedure for shrinkage estimation of CAR scores from high-dimensional data. Subsequently, we conduct a comprehensive comparison study including five advanced regression approaches (boosting, lasso, NEG, MCP, and CAR score) and a univariate approach (marginal correlation) to determine the effectiveness in finding true causal SNPs.ConclusionsSimultaneous SNP selection is a challenging task. We demonstrate that our CAR score-based algorithm consistently outperforms all competing approaches, both uni- and multivariate, in terms of correctly recovered causal SNPs and SNP ranking. An R package implementing the approach as well as R code to reproduce the complete study presented here is available from http://strimmerlab.org/software/care/.

This paper presents a methodology for analyzing Analytic Hierarchy Process (AHP) rankings if the pairwise preference judgments are uncertain (stochastic). If the relative preference statements are represented by judgment intervals, rather than single values, then the rankings resulting from a traditional (deterministic) AHP analysis based on single judgment values may be reversed, and therefore incorrect. In the presence of stochastic judgments, the traditional AHP rankings may be stable or unstable, depending on the nature of the uncertainty. We develop multivariate statistical techniques to obtain both point estimates and confidence intervals of the rank reversal probabilities, and show how simulation experiments can be used as an effective and accurate tool for analyzing the stability of the preference rankings under uncertainty. If the rank reversal probability is low, then the rankings are stable and the decision maker can be confident that the AHP ranking is correct. However, if the likelihood of rank reversal is high, then the decision maker should interpret the AHP rankings cautiously, as there is a subtantial probability that these rankings are incorrect. High rank reversal probabilities indicate a need for exploring alternative problem formulations and methods of analysis. The information about the extent to which the ranking of the alternatives is sensitive to the stochastic nature of the pairwise judgments should be valuable information into the decision‐making process, much like variability and confidence intervals are crucial tools for statistical inference. We provide simulation experiments and numerical examples to evaluate our method. Our analysis of rank reversal due to stochastic judgments is not related to previous research on rank reversal that focuses on mathematical properties inherent to the AHP methodology, for instance, the occurrence of rank reversal if a new alternative is added or an existing one is deleted.