Host genetic variation impacts microbiome composition across human body sites

作者：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 · 发表于：Genome biology · 年份：2015 · DOI：10.1186/s13059-015-0759-1 · 被引用次数：809 · 研究领域：Gut microbiota and health、Epigenetics and DNA Methylation、Immune responses and vaccinations

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 r...