The effect of host genetics on the gut microbiome.

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Abstract

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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Author and article information

Journal

Journal ID (iso-abbrev): Nat. Genet.

Title: Nature genetics

Publisher: Springer Nature

ISSN (Electronic): 1546-1718

ISSN (Print): 1061-4036

Publication date (Electronic): Nov 2016

Volume: 48

Issue: 11

Affiliations

[1 ] University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.

[2 ] Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.

[3 ] Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.

[4 ] Top Institute Food and Nutrition, Wageningen, the Netherlands.

[5 ] Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.

[6 ] University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, the Netherlands.

[7 ] University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.

[8 ] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

[9 ] Department of Computer Science, Aalto University School of Science, Espoo, Finland.

[10 ] Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

[11 ] Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.

[12 ] Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.

[13 ] University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, the Netherlands.

[14 ] University of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Groningen, the Netherlands.

[15 ] Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.

[16 ] Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

[17 ] Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.

Article

Publisher Item ID: ng.3663

DOI: 10.1038/ng.3663

PubMed ID: 27694959

SO-VID: bcb3495c-9d50-458b-8bac-088016194fdb

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