title: Host genetic variation impacts microbiome composition across human body sites.
abstract: BACKGROUND
  The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale.
  
  
  RESULTS
  Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes.
  
  
  CONCLUSIONS
  Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, 55455, USA. blekhman@umn.edu.|Department of Ecology, Evolution, and Behavior, University of Minnesota, St. Paul, MN, 55108, USA. blekhman@umn.edu.
authors.forename: Ran
authors.initials: R
authors.lastname: Blekhman
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.|Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Goodrich
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Huang
authors.affiliation: BRC Bioinformatics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: BRC Bioinformatics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bukowski
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College, London, UK.
authors.forename: Jordana T
authors.initials: JT
authors.lastname: Bell
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College, London, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Alon
authors.initials: A
authors.lastname: Keinan
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.|Department of Microbiology, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.|Current address: Janssen Human Microbiome Institute, Janssen Research and Development, Cambridge, MA, 02142, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Gevers
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
mesh_terms: D001419:Bacteria / Q000145:classification / Q000302:isolation & purification; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D056186:Metagenomics; D064307:Microbiota