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Genome Med. 2018 Jan 29;10(1):6. doi: 10.1186/s13073-018-0515-8.

Host genetic variation and its microbiome interactions within the Human Microbiome Project.

Author information

1
Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge St, Boston, MA, 02114, USA.
2
Department of Biostatistics, Harvard T. H. Chan School of Public Health, 655 Huntington Ave, Boston, MA, 02115, USA.
3
The Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA.
4
Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge St, Boston, MA, 02114, USA.
5
Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge St, Boston, MA, 02114, USA. xavier@molbio.mgh.harvard.edu.
6
The Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA. xavier@molbio.mgh.harvard.edu.
7
Center for Microbiome Informatics & Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. xavier@molbio.mgh.harvard.edu.
8
Department of Biostatistics, Harvard T. H. Chan School of Public Health, 655 Huntington Ave, Boston, MA, 02115, USA. chuttenh@hsph.harvard.edu.
9
The Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA. chuttenh@hsph.harvard.edu.

Abstract

BACKGROUND:

Despite the increasing recognition that microbial communities within the human body are linked to health, we have an incomplete understanding of the environmental and molecular interactions that shape the composition of these communities. Although host genetic factors play a role in these interactions, these factors have remained relatively unexplored given the requirement for large population-based cohorts in which both genotyping and microbiome characterization have been performed.

METHODS:

We performed whole-genome sequencing of 298 donors from the Human Microbiome Project (HMP) healthy cohort study to accompany existing deep characterization of their microbiomes at various body sites. This analysis yielded an average sequencing depth of 32x, with which we identified 27 million (M) single nucleotide variants and 2.3 M insertions-deletions.

RESULTS:

Taxonomic composition and functional potential of the microbiome covaried significantly with genetic principal components in the gastrointestinal tract and oral communities, but not in the nares or vaginal microbiota. Example associations included validation of known associations between FUT2 secretor status, as well as a variant conferring hypolactasia near the LCT gene, with Bifidobacterium longum abundance in stool. The associations of microbial features with both high-level genetic attributes and single variants were specific to particular body sites, highlighting the opportunity to find unique genetic mechanisms controlling microbiome properties in the microbial communities from multiple body sites.

CONCLUSIONS:

This study adds deep sequencing of host genomes to the body-wide microbiome sequences already extant from the HMP healthy cohort, creating a unique, versatile, and well-controlled reference for future studies seeking to identify host genetic modulators of the microbiome.

KEYWORDS:

Association studies; Human Microbiome Project; Human genome sequence; Microbiome and human genetics; Microbiome metagenome sequence

PMID:
29378630
PMCID:
PMC5789541
DOI:
10.1186/s13073-018-0515-8
[Indexed for MEDLINE]
Free PMC Article

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