Genomic sequencing’s value challenged in Stanford study

by jeeg 16. January 2015 20:54

 

The environment may be a much bigger driver of human health than genetics, which raises questions about the value of genomic sequencing and the push toward personalized medicine, says a team of Stanford scientists studying the immune system.

“Genomics technology has advanced so much that we’re seeing an explosion in sequencing and analyzing this and that. Everything starts to look like genetics. And yet, it isn’t, really,” said Mark Davis, lead author of the study and director of Stanford’s Institute for Immunity, Transplantation and Infection. “The big message is the environment matters a lot.”

Davis’ study was specific to the immune system, but it’s likely, he said, that the same environmental influence applies to other body systems for instance, the nervous system and overall health. And while there’s no doubt that genetics plays a huge role in certain diseases and health outcomes, the importance of DNA may be overstated.

Genomic sequencing, which involves reading the genetic makeup of an organism, has become widespread in both research and consumer markets. Scientists are hunting for genetic clues to hundreds of human diseases, from Alzheimer’s and cancer to the flu, and increasingly researchers are promoting the idea of personalized medicine, or targeting treatment to a patient’s DNA.

That’s all valuable work, Davis said. But he’s wary of overselling the potential of genomic sleuthing.

His team recruited 78 identical and 27 fraternal twins who were part of a twin registry built at SRI International in Menlo Park. The siblings, who were between ages 8 and 82, donated blood and other samples, which were tested for 204 different immune system markers, including, for example, the number and variety of certain cells each person has.

Based on the study results, nearly 60 percent of the immune markers were almost totally defined by nongenetic factors — in other words, the environment. And some of the markers became increasingly defined by nongenetic factors with age. Their study was published Thursday in the journal Cell.

Reactions to flu vaccine

One obvious example of environment-over-genetics was in a measurement of the twins’ reactions to a flu vaccine. Siblings had very different immune responses to a vaccine when their blood was analyzed three or four weeks after they were immunized. If their DNA were the dominating driver, scientists would expect twins to have similar, or even identical immune responses.

But, in fact, the twins’ responses were as dissimilar as any two unrelated people, the researchers found. That means that instead of genetics, environmental factors like a person’s previous exposure to certain flu strains are driving the immune response.

The scientists also identified one particular virus — a common pathogen called cytomegalovirus — that has profound effects on the immune system. The virus doesn’t cause illness in most people, who can carry cytomegalovirus their entire lives and never know it, but it can still influence immune markers. In the study, if one twin had been exposed to the virus and the other hadn’t, more than half of their immune markers were dissimilar.

“That’s one single pathogen that can really change the whole structure of the immune system,” Davis said. “Your immune system is almost certainly being shaped by the microbes you come into contact with over your lifetime. That creates an influence on your immunologic makeup that is not gong to be so predictable from genetics.”

Immune system’s job

Davis, along with other experts in immunology and genetics, noted that it’s not surprising the immune system would be so environment-driven.

“The immune system’s entire raison d’être is to sense and react to the environment,” said Mark Seielstad, an associate professor at UCSF’s Institute for Human Genetics, in an e-mail. “Everything that enters our mouth, eyes, ears or bloodstream can and usually does elicit a response, and is 'remembered’ by the adaptive immune system. Even among twins living in nominally similar environments into adulthood, all of these aspects of the environment will differ in many, many ways.”

But Seielstad added that scientists and patients alike should avoid the “temptation” of choosing sides in a genetics-versus-environment debate about most matters of health. They’re both clearly important and work so closely together that it can be tough to untangle which is the dominant player.

In fact, some variation in the immune system may be explained by the complex interactions between environment and genetics, said Jimmie Ye, an assistant professor at UCSF’s Institute for Human Genetics.

“That’s something we’re struggling with because there’s no good way of measuring those interactions,” Ye said. “I hope that this study initiates additional studies looking at interactions, instead of just one or the other.”

David Raulet, chairman of the department of molecular and cell biology at UC Berkeley, said in an e-mail that there is a “large body of evidence that genetic differences affect susceptibility to infections.” He’s also not ready to declare that environment trumps genetics in either the immune system or overall health.

But he noted that there clearly are nongenetic factors at play that are still a mystery to scientists. Even lab animals that are bred to be genetically identical and raised in the same cages can have great variation in immune response, he said.

“Identifying the nongenetic causes of variations in susceptibility to infection is an important problem,” he wrote, “but we have a long way to go.”

Erin Allday , San Francisco Chronicle

 

 

 

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