Host genetic variation impacts microbiome composition across human body sites

By R. Blekhman, Julia Goodrich, Katherine H. Huang, Qi Sun, R. Bukowski, Jordana T. Bell, Tim D. Spector, A. Keinan, Ruth E. Ley, Dirk Gevers and 1 more. Genome Biology, 2015

700 citations recorded by the source corpus.

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. 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. 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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a97280e5bce3bba4ddc80fc36440461fc6d65203

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Citations in the corpus

Genetic determinants of the gut microbiome in UK Twins (2016, unknown): “A second study using the HMP’s human DNA data showed that mitochondrial haplotypes correlated with abundances of specific microbiota in stool (Ma et al., 2014).”
The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “Several studies have reported associations between host genetics and the microbiome (Blekhman et al., 2015; Bonder et al., 2016; Turpin et al., 2016).”
A global interaction network maps a wiring diagram of cellular function (2016, background): “We must also understand the general principles associated with genetic networks involving gain-of-function alleles and more complex genetic interactions that can occur in diploid and polyploid organisms (41), across a variety of different cell types, within whole animals (42–44), or between hosts an”
Understanding the Holobiont: How microbial metabolites affect human health and shape the immune system (2017, background): “Host genetic variation has been shown to be associated with variation in the microbiome composition, but genome-wide approaches to identify individual genes and their role in shaping the microbiome are only beginning to emerge (Blekhman et al., 2015; Spor et al., 2011).”
Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity (2017, background): “…Blaser, 2002; Ley et al., 2005; Turnbaugh et al., 2006; Blaser et al., 2008; Gao et al., 2008; Islami and Kamangar, 2008; Garrett et al., 2010; Tana et al., 2010; Castellarin et al., 2011; Wang et al., 2011; Kostic et al., 2012; Blekhman et al., 2015; O’Keefe et al., 2015; Goodrich et al., 2016).”
Homeostatic immunity and the microbiota (2017, unknown): “Such lines of research should provide insight into the link between host genetic variation in shaping both immunity and the composition of the human microbiome (Blekhman et al., 2015; Goodrich et al., 2014), and provide a starting point towards understanding factors that predict vaccine success.”