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Cited by 745Gut microbiota and healthGenetic Associations and EpidemiologyGenomics and Phylogenetic Studies

Host genetic variation impacts microbiome composition across human body sites

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Blekhman, Ran, Goodrich, Julia K., Huang, Katherine, Sun, Qi, Bukowski, Robert, Bell, Jordana T., Spector, Timothy D., Keinan, Alon +3 more·2015·Genome Biology
DOI 10.1186/s13059-015-0759-1PMC PMC4570153
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Abstract

BACKGROUND: The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. RESULTS: Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. CONCLUSIONS: Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

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  • Host genetic variation is associated with variation in microbiome composition.

    “Host genetic variation has been shown to be associated with variation in the microbiome composition, but genome-wide approaches to identify individual genes and their role in shaping the microbiome are only beginning to emerge (Blekhman et al., 2015; Spor et al., 2011).”

    From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Blekhman et al., 2015

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Authors
Blekhman, R., Goodrich, J. K., Huang, K., Sun, Q., Bukowski, R., Bell, J. T., Spector, T. D., Keinan, A., Ley, R. E., Gevers, D., & Clark, A. G.
Affiliations
  • University of Minnesota (US)
  • Cornell University (US)
  • Broad Institute (US)
  • King's College London (GB)
Corresponding author
Blekhman, Ran
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2015-09-15
Volume
16
Issue
1
Pages
191-191
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-015-0759-1
PMC
PMC4570153
OpenAlex
W1948774627
Cited by
745
References
22
Citations by year
2026: 46 · 2025: 65 · 2024: 42 · 2023: 65 · 2022: 70 · 2021: 87 · 2020: 70 · 2019: 83 · 2018: 71 · 2017: 84 · 2016: 55 · 2015: 5
FWCI
31.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (R01 DK093595, U54 HG004969)
  • Wellcome Trust
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
host genetic variation, human microbiome, microbiota composition, host-microbiome interactions, immune-related genes, inflammatory bowel disease, obesity-related disorders, Human Microbiome Project
MeSH terms
Bacteria, Humans, Genetic Variation, Genome, Human, Metagenomics, Microbiota

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