"We also identified the specific genetic sequence in this gene that serves as a target of that signaling pathway, and we discovered that a well-known variation in that sequence can block that path and disconnect IL6 responses from the effects of stress."
To confirm the biochemical link between misery and death, and the genetic variation that breaks it, the researchers turned to epidemiological studies to prove that carriers of that specific genetic variation were less susceptible to death due to inflammation-related mortality causes under adverse social-environmental conditions.
They found that people with the most common type of the IL6 gene showed an increased risk of death for approximately 11 years after they had been exposed to adverse life events that were strong enough to trigger depression. However, people with the rarer variant of the IL6 gene appeared to be immune to those effects and showed no increase in mortality risk in the aftermath of significant life adversity.
This novel method of discovery using computer modeling and then confirming genetic relationships using test-tube biochemistry, experimental stress studies and human genetic epidemiology could speed the discovery of such gene and environmental relationships, the researchers say.
"Right now, we have to hunt down genetic influences on health through blind searches of huge databases, and the results from that approach have not yielded as much as expected," Cole said. "This study suggests that we can use computer modeling to discover geneenvironment interactions, then confirm them, in order to focus our search more efficiently and hopefully speed the discovery process.
"This opens a new era in which we can begin to understand the influence of adversity on physical health by modeling the basic biology that allows the world outside us to influence the molecular processes going on inside our cells."
|Contact: Mark Wheeler|
University of California - Los Angeles