title: Identifying Host Genetic Variants Associated with Microbiome Composition by Testing Multiple Beta Diversity Matrices.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, Md., USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Hua
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shi
mesh_terms: D003198:Computer Simulation; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008168:Lung / Q000382:microbiology; D064307:Microbiota / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics