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BMC Genomics. 2017 Jul 21;18(1):552. doi: 10.1186/s12864-017-3928-7.

GATE: an efficient procedure in study of pleiotropic genetic associations.

Author information

1
Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.
2
Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, USA.
3
College of Geoscience and Surveying Engineering, China University of Mining and Technology, Beijing, China.
4
Department of Statistics, George Mason University, Fairfax, VA, USA.
5
Rehabilitation Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD, USA.
6
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
7
Department of Mathematics and Statistics, Florida International University, Miami, FL, USA.
8
Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China. liqz@amss.ac.cn.

Abstract

BACKGROUND:

The association studies on human complex traits are admittedly propitious to identify deleterious genetic markers. Compared to single-trait analyses, multiple-trait analyses can arguably make better use of the information on both traits and markers, and thus improve statistical power of association tests prominently. Principal component analysis (PCA) is a well-known useful tool in multivariate analysis and can be applied to this task. Generally, PCA is first performed on all traits and then a certain number of top principal components (PCs) that explain most of the trait variations are selected to construct the test statistics. However, under some situations, only utilizing these top PCs would lead to a loss of important evidences from discarded PCs and thus makes the capability compromised.

METHODS:

To overcome this drawback while keeping the advantages of using the top PCs, we propose a group accumulated test evidence (GATE) procedure. By dividing the PCs which is sorted in the descending order according to the corresponding eigenvalues into a few groups, GATE integrates the information of traits at the group level.

RESULTS:

Simulation studies demonstrate the superiority of the proposed approach over several existing methods in terms of statistical power. Sometimes, the increase of power can reach 25%. These methods are further illustrated using the Heterogeneous Stock Mice data which is collected from a quantitative genome-wide association study.

CONCLUSIONS:

Overall, GATE provides a powerful test for pleiotropic genetic associations.

KEYWORDS:

Biomedical study; Pleiotropic genetic associations; Power; Principal component analysis

PMID:
28732532
PMCID:
PMC5521155
DOI:
10.1186/s12864-017-3928-7
[Indexed for MEDLINE]
Free PMC Article

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