A small ‐sample multivariate kernel machine test for microbiome association studies

ABSTRACT High‐throughput sequencing technologies have enabled large‐scale studies of the role of the human microbiome in health conditions and diseases. Microbial community level association test, as a critical step to establish the connection between overall microbiome composition and an outcome of interest, has now been routinely performed in many studies. However, current microbiome association tests all focus on a single outcome. It has become increasingly common for a microbiome study to collect multiple, possibly related, outcomes to maximize the power of discovery. As these outcomes may share common mechanisms, jointly analyzing these outcomes can amplify the association signal and improve statistical power to detect potential associations. We propose the multivariate microbiome regression‐based kernel association test (MMiRKAT) for testing association between multiple continuous outcomes and overall microbiome composition, where the kernel used in MMiRKAT is based on Bray‐Curtis or UniFrac distance. MMiRKAT directly regresses all outcomes on the microbiome profiles via a semiparametric kernel machine regression framework, which allows for covariate adjustment and evaluates the association via a variance‐component score test. Because most of the current microbiome studies have small sample sizes, a novel small‐sample correction procedure is implemented in MMiRKAT to correct for the conservativeness of the association test when the sample size is small or mo...
Source: Genetic Epidemiology - Category: Epidemiology Authors: Tags: Research Article Source Type: research