title: Genome-Wide Association Studies of the Human Gut Microbiota.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, United States of America.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Davenport
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, United States of America.
authors.forename: Darren A
authors.initials: DA
authors.lastname: Cusanovich
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, United States of America.
authors.forename: Katelyn
authors.initials: K
authors.lastname: Michelini
authors.affiliation: Department of Pediatrics, Saint Justine Hospital Research Centre, Montreal, Canada.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, United States of America.
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, United States of America.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification* / Q000235:genetics; D044822:Biodiversity; D015992:Body Mass Index; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D051379:Mice; D009765:Obesity / Q000235:genetics; D010739:Phospholipase D / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D012336:RNA, Ribosomal, 16S; D010739:Phospholipase D; C106801:phospholipase D1