Challenges and future directions for studying effects of host genetics on the gut microbiome

This Perspective discusses the analytical issues concerning heterogeneity and power encountered in microbial genome-wide association studies and highlights potential future directions for genetic analysis of the microbiome. The human gut microbiome is a complex ecosystem that is involved in its host's metabolism, immunity and health. Although interindividual variations in gut microbial composition are mainly driven by environmental factors, some gut microorganisms are heritable and thus can be influenced by host genetics. In the past 5 years, 12 microbial genome-wide association studies (mbGWAS) with >1,000 participants have been published, yet only a few genetic loci have been consistently confirmed across multiple studies. Here we discuss the state of the art for mbGWAS, focusing on current challenges such as the heterogeneity of microbiome measurements and power issues, and we elaborate on potential future directions for genetic analysis of the microbiome.

Automated summary

This Perspective discusses the analytical challenges of heterogeneity and power in microbial genome-wide association studies (mbGWAS) and suggests potential future directions for genetic analysis of the microbiome. Despite the fact that interindividual variations in gut microbial composition are mainly influenced by environmental factors, some gut microorganisms are heritable and can be affected by host genetics. Although over 12 mbGWAS studies with more than 1,000 participants have been published in the past 5 years, only a few genetic loci have been consistently identified across multiple studies.