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

Nature Genetics volume 54, pages 100–106 (2022)Cite this article

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Abstract

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.

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Fig. 1: Genomic loci reported at genome-wide significance in 12 microbiome GWAS.
Fig. 2: Power analysis for different taxon prevalence.
Fig. 3: Characterizing microbial composition and genetic landscape from MGS.

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Acknowledgements

We thank K. McIntyre for help developing the manuscript. A.Z. is supported by European Research Council Starting grant 715772, Netherlands Organization for Scientific Research (NWO) VIDI grant 016.178.056, CVON grant 806 2018-27 and NWO Gravitation grant ExposomeNL 024.004.017. J.F. is supported by CVON grant 2018-27, European Research Council Consolidator grant 101001678 and NWO VICI grant VI.C.202.022.

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Authors and Affiliations

  1. Institute for Genetic and Biomedical Research (IRGB), National Research Council (CNR), Monserrato, Cagliari, Italy

    Serena Sanna

  2. Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands

    Serena Sanna, Alexander Kurilshikov, Adriaan van der Graaf, Jingyuan Fu & Alexandra Zhernakova

  3. Department of Computational Biology, University of Lausanne, Lausanne, Switzerland

    Adriaan van der Graaf

  4. Department of Pediatrics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands

    Jingyuan Fu

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  1. Serena Sanna
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  2. Alexander Kurilshikov
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Contributions

S.S., A.K., A.v.d.G. and A.Z. performed data analyses; S.S., J.F. and A.Z. wrote the manuscript draft; A.v.d.G. and A.K. provided critical revisions.

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Correspondence to Serena Sanna or Alexandra Zhernakova.

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Sanna, S., Kurilshikov, A., van der Graaf, A. et al. Challenges and future directions for studying effects of host genetics on the gut microbiome. Nat Genet 54, 100–106 (2022). https://doi.org/10.1038/s41588-021-00983-z

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