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

doi:10.1038/s41588-021-00983-z

Review

. 2022 Feb;54(2):100-106.

doi: 10.1038/s41588-021-00983-z. Epub 2022 Feb 3.

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

Serena Sanna^{1

2}, Alexander Kurilshikov³, Adriaan van der Graaf^{3

4}, Jingyuan Fu^{3

5}, Alexandra Zhernakova⁶

Affiliations

¹ Institute for Genetic and Biomedical Research (IRGB), National Research Council (CNR), Monserrato, Cagliari, Italy. serena.sanna@irgb.cnr.it.
² Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. serena.sanna@irgb.cnr.it.
³ Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
⁵ Department of Pediatrics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
⁶ Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. sasha.zhernakova@gmail.com.

PMID: 35115688
DOI: 10.1038/s41588-021-00983-z

Review

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

Serena Sanna et al. Nat Genet. 2022 Feb.

. 2022 Feb;54(2):100-106.

doi: 10.1038/s41588-021-00983-z. Epub 2022 Feb 3.

Authors

Serena Sanna^{1

2}, Alexander Kurilshikov³, Adriaan van der Graaf^{3

4}, Jingyuan Fu^{3

5}, Alexandra Zhernakova⁶

Affiliations

¹ Institute for Genetic and Biomedical Research (IRGB), National Research Council (CNR), Monserrato, Cagliari, Italy. serena.sanna@irgb.cnr.it.
² Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. serena.sanna@irgb.cnr.it.
³ Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
⁵ Department of Pediatrics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
⁶ Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. sasha.zhernakova@gmail.com.

PMID: 35115688
DOI: 10.1038/s41588-021-00983-z

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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References

1. Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016). - PubMed - DOI
1. Kurilshikov, A. et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat. Genet. 53, 156–165 (2021). - PubMed - PMC - DOI
1. Lopera-Maya, E. A. et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nat. Genet. https://doi.org/10.1038/s41588-021-00992-y (2022).
1. Gacesa, R. et al. The Dutch Microbiome Project defines factors that shape the healthy gut microbiome. Preprint at bioRxiv https://doi.org/10.1101/2020.11.27.401125 (2020).
1. Qin, Y. et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat. Genet. https://doi.org/10.1038/s41588-021-00991-z (2022).

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[1] Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016). - PubMed - DOI

[2] Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016). - PubMed - DOI

[3] Kurilshikov, A. et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat. Genet. 53, 156–165 (2021). - PubMed - PMC - DOI

[4] Kurilshikov, A. et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat. Genet. 53, 156–165 (2021). - PubMed - PMC - DOI

[5] Lopera-Maya, E. A. et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nat. Genet. https://doi.org/10.1038/s41588-021-00992-y (2022).

[6] Lopera-Maya, E. A. et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nat. Genet. https://doi.org/10.1038/s41588-021-00992-y (2022).

[7] Gacesa, R. et al. The Dutch Microbiome Project defines factors that shape the healthy gut microbiome. Preprint at bioRxiv https://doi.org/10.1101/2020.11.27.401125 (2020).

[8] Gacesa, R. et al. The Dutch Microbiome Project defines factors that shape the healthy gut microbiome. Preprint at bioRxiv https://doi.org/10.1101/2020.11.27.401125 (2020).

[9] Qin, Y. et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat. Genet. https://doi.org/10.1038/s41588-021-00991-z (2022).

[10] Qin, Y. et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat. Genet. https://doi.org/10.1038/s41588-021-00991-z (2022).

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

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

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