Host genetic variation impacts microbiome composition across human body sites

Ran Blekhman, Julia K. Goodrich, Katherine Huang, Qi Sun, Robert Bukowski, Jordana T. Bell, Timothy D. Spector, Alon Keinan, Ruth E. Ley, Dirk Gevers, Andrew G. Clark

Research output: Contribution to journalArticlepeer-review

385 Scopus citations

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.

Original languageEnglish (US)
Article number191
JournalGenome biology
Volume16
Issue number1
DOIs
StatePublished - Sep 15 2015

Bibliographical note

Funding Information:
We thank the members of the Blekhman, Clark, Ley, and Keinan labs for discussions; O. Koren, T. Connallon, A. Early, L. Ma, and C. Van Hout for comments on the manuscript; and the Human Microbiome Project for the publically available data analyzed in this study. The work was supported by grant R01 DK093595 to REL and AGC. DG and KH were supported by a grant from the NIH (NIH U54 HG004969). The TwinsUK study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The TwinsUK study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. TDS is holder of an ERC Advanced Principal Investigator award. SNP genotyping of TwinsUK individuals was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/ CIDR. This work was carried out in part using computing resources at the University of Minnesota Supercomputing Institute.

Publisher Copyright:
© 2015 Blekhman et al.

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