IT’S IN THE GENES
By Jef Akst
– Researchers find strong correlations between the composition of the human microbiome and genetic variation in immune-related pathways.
Scouring the genomes and body-wide microbial communities of 93 people, researchers have discovered a link between the composition of the microbiome and genetic variation in innate immunity, phagocyte function, and other immune pathways. The research was presented by University of Minnesota population geneticist Ran Blekhman today (October 24) at the American Society of Human Genetics 2013 annual meeting in Boston.
“This is cool stuff,” Lita Proctor from the National Human Genome Research Institute wrote in an e-mail to The Scientist. “This study is the one of the first documenting the relationship between microbiome composition and the human genome.”
Other researchers have linked specific gene variants to alterations in the human microbiome, noted George Weinstock of The Genome Institute at Washington University, whose own work has shown that host-microbe interactions are influenced by genes involved in drug metabolism. This study, however, may well be the first genome-wide search for such variants in humans, and “genetic variation in mouse does not represent genetic variation that segregates in human populations,” Blekhman noted.
While working as a postdoc in Andrew Clark’s lab at Cornell University, Blekhman knew that the composition of the microbiome was linked to various diseases, like diabetes, and that such diseases had also been shown to have a genetic component. So he was curious to learn how the microbiome is connected to the genes of the host.
To answer this question, he and his colleagues turned to the Human Microbiome Project, led by Proctor, which has produced publically available data on individuals’ microbiomes from 15 different body sites, including the gut, skin, and mouth. The composition of the microbiomes had been determined by metagenomic shotgun sequencing — the sequencing of all the genetic material in a sample — so in addition to the bacterial DNA, the project had also collected and sequenced bits of the host genome. Normally these host data are simply cast aside, but upon aligning the sequences to the host genome, “we can actually get pretty good genome-wide coverage,” Blekhman said about 10-times coverage of the entire host genome.
The team first looked for overall correlations between host genetic variation and microbiome composition, finding “pretty significant correlations” in 10 of the 15 body sites. “Individuals with more similar genomes have more similar microbiomes,” Blekhman said. But without controlling for potential confounding variables, like diet, the researchers couldn’t be sure whether the correlations were truly a result of genetics, or if they were influenced by environmental factors. So the next step was the more stringent analysis of looking for correlations between single nucleotide polymorphisms (SNPs) and microbiome composition.
The researchers did identify hundreds of correlations in the millions of SNPs they looked at… read more
Source: The Scientist
Photo: Immune cells surrounding hair follicles in mouse skin. These hair follicles are home to a diverse array of commensal bacteria. Source: FLICKR, NIAID