The effect of host genetics on the gut microbiome
Open accessAbstract
The gut microbiome is affected by multiple factors, including genetics. In this study, we assessed the influence of host genetics on microbial species, pathways and gene ontology categories, on the basis of metagenomic sequencing in 1,514 subjects. In a genome-wide analysis, we identified associations of 9 loci with microbial taxonomies and 33 loci with microbial pathways and gene ontology terms at P < 5 × 10-8. Additionally, in a targeted analysis of regions involved in complex diseases, innate and adaptive immunity, or food preferences, 32 loci were identified at the suggestive level of P < 5 × 10-6. Most of our reported associations are new, including genome-wide significance for the C-type lectin molecules CLEC4F-CD207 at 2p13.3 and CLEC4A-FAM90A1 at 12p13. We also identified association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 × 10-8) and provide evidence of a gene-diet interaction in the regulation of Bifidobacterium abundance. Our results demonstrate the importance of understanding host-microbe interactions to gain better insight into human health.
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Studies have found evidence for heritability of relative bacterial abundances or specific taxa.
“with studies finding evidence for heritability of relative bacterial abundances or specific taxa [15, 63–68]”
From Population structure of human gut bacteria in a diverse cohort from rural Tanzania and Botswana (2019) · cites this paper as [67]
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- Authors
- Bonder, M. J., Kurilshikov, A., Tigchelaar, E. F., Mujagic, Z., Imhann, F., Vila, A. V., Deelen, P., Vatanen, T., Schirmer, M., Smeekens, S. P., Zhernakova, D. V., Jankipersadsing, S. A., Jaeger, M., Oosting, M., Cenit, M. C., Masclee, A. A. M., Swertz, M. A., Li, Y., Kumar, V., Joosten, L., Harmsen, H., Weersma, R. K., Franke, L., Hofker, M. H., Xavier, R. J., Jonkers, D., Netea, M. G., Wijmenga, C., Fu, J., & Zhernakova, A.
- Affiliations
- University Medical Center Groningen (NL)
- Maastricht University Medical Centre (NL)
- Broad Institute (US)
- Radboud University Medical Center (NL)
- Corresponding author
- Wijmenga, Cisca
- Fu, Jingyuan
- Zhernakova, Alexandra
- ORCID
- Bonder, Marc Jan
- Kurilshikov, Alexander
- Mujagic, Zlatan
- Imhann, Floris
- Vila, Arnau Vich
- Deelen, Patrick
- Vatanen, Tommi
- Schirmer, Melanie
- Smeekens, Sanne P
- Zhernakova, Daria V
- Jankipersadsing, Soesma A
- Jaeger, Martin
- Oosting, Marije
- Masclee, Ad A M
- Swertz, Morris A
- Li, Yang
- Kumar, Vinod
- Joosten, Leo
- Harmsen, Hermie
- Weersma, Rinse K
- Franke, Lude
- Xavier, Ramnik J
- Jonkers, Daisy
- Netea, Mihai G
- Wijmenga, Cisca
- Fu, Jingyuan
- Zhernakova, Alexandra
- Venue
- Nature Genetics
- Published
- 2016-10-03
- Volume
- 48
- Issue
- 11
- Pages
- 1407-1412
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2528524934
- Cited by
- 819
- References
- 88
- Citations by year
- 2026: 44 · 2025: 71 · 2024: 83 · 2023: 94 · 2022: 91 · 2021: 91 · 2020: 104 · 2019: 112 · 2018: 58 · 2017: 63 · 2016: 7
- FWCI
- 41.59
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- European Commission (322698, FP7/2007–2013/ERC, 2007–2013, FP7 2007-2013, 310372, FP7/2007, 259867)
- Rijksuniversiteit Groningen
- ZonMw (016.136.308, VIDI 864.13.013, 917.14.374)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (FP7 2007-2013, NWO-VIDI 864.13.013, ZonMW-VIDI 016.136.308, 863.13.011, 864.13.013, 917.14.374, 2012-322698, 016.136.308, 637640, ZonMW-VIDI 917.14.374)
- 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 › Genetics › Nutrition, Genetics, and Disease
- Keywords
- gut microbiota, host genetics, gene-diet interaction, LCT gene, Bifidobacterium, C-type lectin, host-microbe interactions, microbial pathways, metagenomics
- MeSH terms
- Gastrointestinal Microbiome, Adolescent, Adult, Aged, Animals, Female, Humans, Immunity, Male, Middle Aged, Cohort Studies, Genome, Human, Polymorphism, Single Nucleotide, Mice, Genome-Wide Association Study, Young Adult
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