Genome-Wide Association Studies of the Human Gut Microbiota

The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one 2015-11, Vol.10 (11), p.e0140301-e0140301
Main Authors:	Davenport, Emily R, Cusanovich, Darren A, Michelini, Katelyn, Barreiro, Luis B, Ober, Carole, Gilad, Yoav
Format:	Article
Language:	eng
Subjects:	Abundance Animal tissues Animals Antibiotics Bacteria Bacteria - classification Bacteria - genetics Biodiversity Body mass Body Mass Index Body size Chromatin Chromosomes Disease Faecalibacterium Fecal microflora Feces - microbiology Female Gastroenterology Gastrointestinal Microbiome - genetics Gastrointestinal Tract - microbiology Gene mapping Genes Genetic diversity Genetic effects Genetics Genome-Wide Association Study Genomes Genotypes Humans Inflammatory bowel disease Intestinal microflora Male Mice Microbiomes Microbiota Microbiota (Symbiotic organisms) Obesity Obesity - genetics Phospholipase D - genetics Polymorphism, Single Nucleotide Quantitative genetics Quantitative trait loci Quantitative Trait Loci - genetics Relative abundance RNA, Ribosomal, 16S - genetics Single nucleotide polymorphisms Single-nucleotide polymorphism Studies Summer Taxa Winter
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.
ISSN:	1932-6203 1932-6203