Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort
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Abstract
Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.
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Lactase-persistence alleles at the LCT gene consistently track with higher abundances of Bifidobacterium spp.
“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 [62]
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- Authors
- Qin, Y., Havulinna, A. S., Liu, Y., Jousilahti, P., Ritchie, S. C., Tokolyi, A., Sanders, J. G., Valsta, L., Brożyńska, M., Zhu, Q., Tripathi, A., Vázquez-Baeza, Y., Loomba, R., Cheng, S., Jain, M., Niiranen, T., Lahti, L., Knight, R., Salomaa, V., Inouye, M., & Méric, G.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Finnish Institute for Health and Welfare (FI)
- Wellcome Sanger Institute (GB)
- Cornell University (US)
- University of California San Diego (US)
- Cedars-Sinai Medical Center (US)
- University of Turku (FI)
- Corresponding author
- Inouye, Michael
- Méric, Guillaume
- ORCID
- Venue
- Nature Genetics
- Published
- 2022-02
- Volume
- 54
- Issue
- 2
- Pages
- 134-142
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC9883041
- OpenAlex
- W4225854522
- Cited by
- 586
- References
- 131
- Citations by year
- 2026: 115 · 2025: 185 · 2024: 135 · 2023: 95 · 2022: 53 · 2021: 3
- FWCI
- 39.31
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-02-29)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Genetics (publishedVersion)
- medRxiv (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- U.S. Department of Defense (5UL1TR001442, W81XWH, W81XWH1820026, W81XWH-18)
- Foundation for Cardiovascular Research
- Suomen Lääketieteen Säätiö
- Wellcome Trust
- Scottish Government
- European Bioinformatics Institute
- National Institute for Health and Care Research (BRC1215-20014)
- British Heart Foundation (RG/13/13/30194; RG/18/13/33946, RG/18/13/33946, RG/13/13/30194)
- Department of Health and Social Care
- University of Cambridge (BRC-1215-20014)
- Public Health Agency
- Academy of Finland (#321356, 295741, 321351)
- Cambridge University Hospitals
- State Government of Victoria
- Emil Aaltosen Säätiö (321351)
- Sydäntutkimussäätiö
- Paavo Nurmen Säätiö
- National Institutes of Health (UL1TR001442)
- Horizon 2020 Framework Programme (952914)
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Medical Research Council (RG/13/13/30194, BRC-1215-20014, MR/L003120, MR/L003120/1)
- Engineering and Physical Sciences Research Council (H2020)
- Economic and Social Research Council
- Health and Social Care Research and Development Division
- NIHR Cambridge Biomedical Research Centre ((BRC-1215-20014))
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124318, R01DK121378, R01DK106419, P30DK120515, U01DK061734)
- National Institute of Environmental Health Sciences (P42ES010337)
- National Center for Advancing Translational Sciences
- DOD Peer Reviewed Cancer Research Program
- Health Data Research UK
- 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, diet, host-microbiota interactions, Bifidobacterium, dairy consumption, ABO blood group system, Enterococcus faecalis, MED13L, Morganella, major depressive disorder, colorectal cancer, metagenomics, Mendelian randomization, Finnish population
- MeSH terms
- ABO Blood-Group System, Eubacteriales, Gastrointestinal Microbiome, Host Microbial Interactions, Bifidobacterium, Major Depressive Disorder, Diet, Dietary Fiber, Humans, Enterococcus faecalis, Genetic Variation, Colorectal Neoplasms, Cohort Studies, Morganella, Polymorphism, Single Nucleotide, Gastrointestinal Tract, Lactase, Metagenome, Genome-Wide Association Study, Mediator Complex, Mendelian Randomization Analysis
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