title: Comparison of parametric and machine methods for variable selection in simulated Genetic Analysis Workshop 19 data.
abstract: Current findings from genetic studies of complex human traits often do not explain a large proportion of the estimated variation of these traits due to genetic factors. This could be, in part, due to overly stringent significance thresholds in traditional statistical methods, such as linear and logistic regression. Machine learning methods, such as Random Forests (RF), are an alternative approach to identify potentially interesting variants. One major issue with these methods is that there is no clear way to distinguish between probable true hits and noise variables based on the importance metric calculated. To this end, we are developing a method called the Relative Recurrency Variable Importance Metric (r2VIM), a RF-based variable selection method. Here, we apply r2VIM to the unrelated Genetic Analysis Workshop 19 data with simulated systolic blood pressure as the phenotype. We compare the number of "true" functional variants identified by r2VIM with those identified by linear regression analyses that use a Bonferroni correction to calculate a significance threshold. Our results show that r2VIM performed comparably to linear regression. Our findings are proof-of-concept for r2VIM, as it identifies a similar number of functional and nonfunctional variants as a more commonly used technique when the optimal importance score threshold is used.
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Holzinger
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA ; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Christian-Albrechts-Platz 4, 24118 Kiel, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.affiliation: Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, 9000 Rockville Pike, Building 12A, Bethesda, MD 20892 USA.
authors.forename: James
authors.initials: J
authors.lastname: Malley
authors.affiliation: Center for Inherited Disease Research, IGM, Johns Hopkins School of Medicine, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Pugh
authors.affiliation: Center for Inherited Disease Research, IGM, Johns Hopkins School of Medicine, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.affiliation: Center for Inherited Disease Research, IGM, Johns Hopkins School of Medicine, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Griffith
authors.affiliation: Center for Inherited Disease Research, IGM, Johns Hopkins School of Medicine, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Cropp
authors.affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, MD 21224 USA.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson