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Hum Hered. 2016;81(2):117-126. doi: 10.1159/000448733. Epub 2017 Jan 12.

Identifying Host Genetic Variants Associated with Microbiome Composition by Testing Multiple Beta Diversity Matrices.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Md., USA.

Abstract

OBJECTIVES:

Host genetics have been recently reported to affect human microbiome composition. We previously developed a statistical framework, microbiomeGWAS, to identify host genetic variants associated with microbiome composition by testing a distance matrix. However, statistical power depends on the choice of a microbiome distance matrix. To achieve more robust statistical power, we aim to extend microbiomeGWAS to test the association with many distance matrices, which are defined based on multilevel taxa abundances and phylogenetic information.

METHODS:

The main challenge is to accurately and rapidly evaluate the significance for millions of SNPs. We propose methods for approximating p values by correcting for the multiple testing introduced by testing many distance matrices and by correcting for the skewness and kurtosis of score statistics.

RESULTS:

The accuracy of p value approximation was verified by simulations. We applied our method to a set of 147 lung cancer patients with 16S rRNA microbiome profiles from nonmalignant lung tissues. We show that correcting for skewness and kurtosis eliminated dramatic deviations in the quantile-quantile plot.

CONCLUSION:

We developed computationally efficient methods for identifying host genetic variants associated with microbiome composition by testing many distance matrices. The algorithms are implemented in the package microbiomeGWAS (https://github.com/lsncibb/microbiomeGWAS).

PMID:
28076867
PMCID:
PMC6540989
DOI:
10.1159/000448733
[Indexed for MEDLINE]
Free PMC Article

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