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Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project
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Abstract
Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10−10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10−8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome. A genome-wide association study of 207 taxa and 205 pathways representing gut microbial composition and function from 7,738 individuals of the Dutch Microbiome Project identifies genetic associations at the LCT and ABO loci.
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“Lactase-persistence alleles at the LCT gene consistently track with higher abundances of Bifidobacterium spp.,61,62”
From Gut dysbiosis in oncology: a risk factor for immunoresistance (2026) · cites this paper as [61]
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Metadata
- Authors
- Lopera-Maya, E. A., Kurilshikov, A., van der Graaf, A., Hu, S., Andreu-Sánchez, S., Chen, L., Vila, A. V., Gacesa, R., Sinha, T., Collij, V., Klaassen, M. A. Y., Bolte, L. A., Gois, M. F. B., Neerincx, P. B. T., Swertz, M. A., Study, L. C., Aguirre-Gamboa, R., Deelen, P., Franke, L., Kuivenhoven, J. A., Lopera-Maya, E. A., Nolte, I. M., Sanna, S., Snieder, H., Swertz, M. A., Vonk, J. M., Wijmenga, C., Harmsen, H. J. M., Wijmenga, C., Fu, J., Weersma, R. K., Zhernakova, A., & Sanna, S.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- Zhernakova, Alexandra
- ORCID
- Kurilshikov, Alexander
- van der Graaf, Adriaan
- Hu, Shixian
- Andreu-Sánchez, Sergio
- Chen, Lianmin
- Vila, Arnau Vich
- Gacesa, Ranko
- Sinha, Trishla
- Collij, Valerie
- Bolte, Laura A.
- Gois, Milla F. Brandao
- Neerincx, Pieter B. T.
- Deelen, Patrick
- Franke, Lude
- Kuivenhoven, Jan A.
- Nolte, Ilja M.
- Snieder, Harold
- Vonk, Judith M.
- Harmsen, Hermie J. M.
- Fu, Jingyuan
- Weersma, Rinse K.
- Zhernakova, Alexandra
- Venue
- Nature Genetics
- Published
- 2022-02
- Volume
- 54
- Issue
- 2
- Pages
- 143-151
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W4225566784
- Cited by
- 553
- References
- 84
- Citations by year
- 2026: 107 · 2025: 153 · 2024: 156 · 2023: 105 · 2022: 28
- FWCI
- 39.64
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-07-25)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Genetics (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS)
- Seerave Foundation (715772, 2018-27, 016.178.056)
- Stichting De Cock-Hadders (20:20-13)
- Rijksuniversiteit Groningen (2018-27, 715772)
- Ministerie van Volksgezondheid, Welzijn en Sport (024.003.001)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO Gravitation grant Exposome-NL 024.004.017, NWO SPI 92–266, 024.003.001, Exposome‐NL 024.004.017, 024.003, 016.178.056, 016.Vidi.178.056, 024.004.017, SPI 92-266)
- China Scholarship Council (024.004.017, CSC 201708320268)
- Universitair Medisch Centrum Groningen
- Interreg (202085)
- H2020 European Research Council (101001678, 715772)
- 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
- host genetics, gut microbiota, microbial community composition, microbial function, LCT gene, ABO gene, lactose intake, genetic association
- MeSH terms
- ABO Blood-Group System, Gastrointestinal Microbiome, Host Microbial Interactions, Galactoside 2-alpha-L-fucosyltransferase, Bifidobacterium, Diet, Fucosyltransferases, Humans, Netherlands, Triglycerides, Genetic Variation, Genome, Human, Sodium Chloride, Dietary, Bacterial Physiological Phenomena, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Gastrointestinal Tract, Lactase, Metabolic Networks and Pathways, Metagenome, Genome-Wide Association Study
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