Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort
Authors
Qin, Youwen
Havulinna, Aki
Liu, Yang
Jousilahti, Pekka
Tokolyi, Alex
Sanders, Jon
Valsta, Liisa
Brożyńska, Marta
Zhu, Qiyun
Tripathi, Anupriya
Vazquez-Baeza, Yoshiki
Loomba, Rohit
Cheng, Susan
Jain, Mohit
Niiranen, Teemu
Lahti, Leo
Knight, Rob
Salomaa, Veikko
Méric, Guillaume
Journal Title
Nature Genetics
ISSN
1061-4036
Publisher
Nature Research
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Qin, Y., Havulinna, A., Liu, Y., Jousilahti, P., Ritchie, S., Tokolyi, A., Sanders, J., et al. (). Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nature Genetics https://doi.org/10.1038/s41588-021-00991-z
Abstract
Co-evolution between humans and the microbial communities colonizing them has resulted in an intimate assembly of thousands of microbial species mutualistically living on and in their body and impacting multiple aspects of host physiology and health. Several studies examining whether human genetic variation can affect gut microbiota suggest a complex combination of environmental and host factors. Here, we leverage a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial shotgun metagenomes, dietary information and health records up to 16 years post-sampling, to characterize human genetic variations associated with microbial abundances, and predict possible causal links with various diseases using Mendelian randomization (MR). Genome-wide association study (GWAS) identified 583 independent SNP-taxon associations at genome-wide significance ( p <5.0×10 -8 ), which included notable strong associations with LCT ( p =5.02×10 -35 ), ABO ( p =1.1×10 -12 ), and MED13L ( p =1.84×10 -12 ). A combination of genetics and dietary habits was shown to strongly shape the abundances of certain key bacterial members of the gut microbiota, and explain their genetic association. Genetic effects from the LCT locus on Bifidobacterium and three other associated taxa significantly differed according to dairy intake. Variation in mucin-degrading Faecalicatena lactaris abundances were associated with ABO , highlighting a preferential utilization of secreted A/B/AB-antigens as energy source in the gut, irrespectively of fibre intake. Enterococcus faecalis levels showed a robust association with a variant in MED13L , with putative links to colorectal cancer. Finally, we identified putative causal relationships between gut microbes and complex diseases using MR, with a predicted effect of Morganella on major depressive disorder that was consistent with observational incident disease analysis. Overall, we present striking examples of the intricate relationship between humans and their gut microbial communities, and highlight important health implications.
Embargo Lift Date
2022-08-03
Identifiers
External DOI: https://doi.org/10.1038/s41588-021-00991-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332870
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