A novel algorithm for simultaneous SNP selection in high-dimensional genome-wide association studies.

Abstract:

BACKGROUND:Identification 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. RESULTS:We 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. CONCLUSIONS:Simultaneous 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/.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Zuber V,Duarte Silva AP,Strimmer K

doi

10.1186/1471-2105-13-284

subject

Has Abstract

pub_date

2012-10-31 00:00:00

pages

284

issn

1471-2105

pii

1471-2105-13-284

journal_volume

13

pub_type

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