Host genetic variation and its microbiome interactions within the Human Microbiome Project
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...
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doaj-9f77dd7d32cc455cb0c8cff2c11a9a8a2020-11-24T21:17:09ZengBMCGenome Medicine1756-994X2018-01-0110111310.1186/s13073-018-0515-8Host genetic variation and its microbiome interactions within the Human Microbiome ProjectRaivo Kolde0Eric A. Franzosa1Gholamali Rahnavard2Andrew Brantley Hall3Hera Vlamakis4Christine Stevens5Mark J. Daly6Ramnik J. Xavier7Curtis Huttenhower8Center for Computational and Integrative Biology, Massachusetts General HospitalDepartment of Biostatistics, Harvard T. H. Chan School of Public HealthDepartment of Biostatistics, Harvard T. H. Chan School of Public HealthThe Broad Institute of MIT and HarvardThe Broad Institute of MIT and HarvardThe Broad Institute of MIT and HarvardThe Broad Institute of MIT and HarvardCenter for Computational and Integrative Biology, Massachusetts General HospitalDepartment of Biostatistics, Harvard T. H. Chan School of Public HealthAbstract 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.http://link.springer.com/article/10.1186/s13073-018-0515-8Human Microbiome ProjectMicrobiome and human geneticsHuman genome sequenceMicrobiome metagenome sequenceAssociation studies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Raivo Kolde Eric A. Franzosa Gholamali Rahnavard Andrew Brantley Hall Hera Vlamakis Christine Stevens Mark J. Daly Ramnik J. Xavier Curtis Huttenhower |
spellingShingle |
Raivo Kolde Eric A. Franzosa Gholamali Rahnavard Andrew Brantley Hall Hera Vlamakis Christine Stevens Mark J. Daly Ramnik J. Xavier Curtis Huttenhower Host genetic variation and its microbiome interactions within the Human Microbiome Project Genome Medicine Human Microbiome Project Microbiome and human genetics Human genome sequence Microbiome metagenome sequence Association studies |
author_facet |
Raivo Kolde Eric A. Franzosa Gholamali Rahnavard Andrew Brantley Hall Hera Vlamakis Christine Stevens Mark J. Daly Ramnik J. Xavier Curtis Huttenhower |
author_sort |
Raivo Kolde |
title |
Host genetic variation and its microbiome interactions within the Human Microbiome Project |
title_short |
Host genetic variation and its microbiome interactions within the Human Microbiome Project |
title_full |
Host genetic variation and its microbiome interactions within the Human Microbiome Project |
title_fullStr |
Host genetic variation and its microbiome interactions within the Human Microbiome Project |
title_full_unstemmed |
Host genetic variation and its microbiome interactions within the Human Microbiome Project |
title_sort |
host genetic variation and its microbiome interactions within the human microbiome project |
publisher |
BMC |
series |
Genome Medicine |
issn |
1756-994X |
publishDate |
2018-01-01 |
description |
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. |
topic |
Human Microbiome Project Microbiome and human genetics Human genome sequence Microbiome metagenome sequence Association studies |
url |
http://link.springer.com/article/10.1186/s13073-018-0515-8 |
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