Document Type

Article

Publication Date

8-2021

Publication Title

Mammalian genome : official journal of the International Mammalian Genome Society

Keywords

JMG, JGM

JAX Source

Mamm Genome 2021 Aug; 32(4):263-281

Volume

32

Issue

4

First Page

263

Last Page

281

ISSN

1432-1777

PMID

34159422

DOI

https://doi.org/10.1007/s00335-021-09884-2

Grant

DA043809, D039841

Abstract

The gut microbiome plays a significant role in health and disease, and there is mounting evidence indicating that the microbial composition is regulated in part by host genetics. Heritability estimates for microbial abundance in mice and humans range from (0.05-0.45), indicating that 5-45% of inter-individual variation can be explained by genetics. Through twin studies, genetic association studies, systems genetics, and genome-wide association studies (GWAS), hundreds of specific host genetic loci have been shown to associate with the abundance of discrete gut microbes. Using genetically engineered knock-out mice, at least 30 specific genes have now been validated as having specific effects on the microbiome. The relationships among of host genetics, microbiome composition, and abundance, and disease is now beginning to be unraveled through experiments designed to test causality. The genetic control of disease and its relationship to the microbiome can manifest in multiple ways. First, a genetic variant may directly cause the disease phenotype, resulting in an altered microbiome as a consequence of the disease phenotype. Second, a genetic variant may alter gene expression in the host, which in turn alters the microbiome, producing the disease phenotype. Finally, the genetic variant may alter the microbiome directly, which can result in the disease phenotype. In order to understand the processes that underlie the onset and progression of certain diseases, future research must take into account the relationship among host genetics, microbiome, and disease phenotype, and the resources needed to study these relationships.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

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